Pub Date : 2025-03-01DOI: 10.1016/j.micinf.2024.105464
Jeremia M. Coish , Lori A. MacNeil , Adam J. MacNeil
Antibody-dependent enhancement (ADE) is an immunological paradox whereby sensitization following a primary viral infection results in the subsequent enhancement of a similar secondary infection. This idiosyncratic immune response has been established in dengue virus infections, driven by four antigenically related serotypes co-circulating in endemic regions. Several coronaviruses exhibit antibody-mediated mechanisms of viral entry, which has led to speculation of an ADE capacity for SARS-CoV-2, though in vivo and epidemiological evidence do not currently support this phenomenon. Three distinct antibody-dependent mechanisms for SARS-CoV-2 entry have recently been demonstrated: 1. FcR-dependent, 2. ACE2-FcR-interdependent, and 3. FcR-independent. These mechanisms of viral entry may be dependent on SARS-CoV-2 antibody specificity; antibodies targeting the receptor binding domain (RBD) typically result in Fc-dependent and ACE2-FcR-interdependent entry, whereas antibodies targeting the N-terminal domain can induce a conformational change to the RBD that optimizes ACE2-receptor binding domain interactions independent of Fc receptors. Whether these antibody-dependent entry mechanisms of SARS-CoV-2 result in the generation of infectious progenies and enhancement of infection has not been robustly demonstrated. Furthermore, ADE of SARS-CoV-2 mediated by antigenic seniority remains a theoretical concern, as no evidence suggests that SARS-CoV-2 imprinting blunts a subsequent immune response, contributing to severe COVID-19 disease.
{"title":"The SARS-CoV-2 antibody-dependent enhancement façade","authors":"Jeremia M. Coish , Lori A. MacNeil , Adam J. MacNeil","doi":"10.1016/j.micinf.2024.105464","DOIUrl":"10.1016/j.micinf.2024.105464","url":null,"abstract":"<div><div>Antibody-dependent enhancement (ADE) is an immunological paradox whereby sensitization following a primary viral infection results in the subsequent enhancement of a similar secondary infection. This idiosyncratic immune response has been established in dengue virus infections, driven by four antigenically related serotypes co-circulating in endemic regions. Several coronaviruses exhibit antibody-mediated mechanisms of viral entry, which has led to speculation of an ADE capacity for SARS-CoV-2, though <em>in vivo</em> and epidemiological evidence do not currently support this phenomenon. Three distinct antibody-dependent mechanisms for SARS-CoV-2 entry have recently been demonstrated: 1. FcR-dependent, 2. ACE2-FcR-interdependent, and 3. FcR-independent. These mechanisms of viral entry may be dependent on SARS-CoV-2 antibody specificity; antibodies targeting the receptor binding domain (RBD) typically result in Fc-dependent and ACE2-FcR-interdependent entry, whereas antibodies targeting the N-terminal domain can induce a conformational change to the RBD that optimizes ACE2-receptor binding domain interactions independent of Fc receptors. Whether these antibody-dependent entry mechanisms of SARS-CoV-2 result in the generation of infectious progenies and enhancement of infection has not been robustly demonstrated. Furthermore, ADE of SARS-CoV-2 mediated by antigenic seniority remains a theoretical concern, as no evidence suggests that SARS-CoV-2 imprinting blunts a subsequent immune response, contributing to severe COVID-19 disease.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 3","pages":"Article 105464"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.micinf.2024.105434
Georgina Nyawo , Charissa C. Naidoo , Benjamin G. Wu , Benjamin Kwok , Jose C. Clemente , Yonghua Li , Stephanie Minnies , Byron Reeve , Suventha Moodley , Thadathilankal-Jess John , Sumanth Karamchand , Shivani Singh , Alfonso Pecararo , Anton Doubell , Charles Kyriakakis , Robin Warren , Leopoldo N. Segal , Grant Theron
Background
The site-of-disease microbiome and predicted metagenome were evaluated in a cross-sectional study involving people with presumptive tuberculous pericarditis. We also explored the interaction between C-reactive protein (CRP) and the microbiome.
Methods
People with effusions requiring diagnostic pericardiocentesis (n=139) provided pericardial fluid for sequencing and blood for CRP measurement.
Results
Pericardial fluid microbiota differed in β-diversity among people with definite (dTB, n=91), probable (pTB, n=25), and non- (nTB, n=23) tuberculous pericarditis. dTBs were Mycobacterium-, Lacticigenium-, and Kocuria-enriched vs. nTBs. HIV-positive dTBs were Mycobacterium-, Bifidobacterium-, Methylobacterium-, and Leptothrix-enriched vs. HIV-negative dTBs. HIV-positive dTBs on ART were Mycobacterium- and Bifidobacterium-depleted vs. those not on ART. dTBs exhibited enrichment in short-chain fatty acid (SCFA) and mycobacterial metabolism pathways vs. nTBs. Additional non-pericardial involvement (pulmonary infiltrates) was associated with Mycobacterium-enrichment and Streptococcus-depletion. Mycobacterium reads were in 34 % (31/91) of dTBs, 8 % (2/25) of pTBs and 17 % (4/23) nTBs. People with CRP above (vs. below) the median value had different β-diversity (Pseudomonas-depleted). No correlation was found between enriched taxa in dTBs and CRP.
Conclusions
Pericardial fluid microbial composition varies by tuberculosis status, HIV (and ART) status and dTBs are enriched in SCFA-associated taxa. The clinical significance, including mycobacterial reads in nTBs and pTBs, requires evaluation.
{"title":"Bad company? The pericardium microbiome in people investigated for tuberculous pericarditis in an HIV-prevalent setting","authors":"Georgina Nyawo , Charissa C. Naidoo , Benjamin G. Wu , Benjamin Kwok , Jose C. Clemente , Yonghua Li , Stephanie Minnies , Byron Reeve , Suventha Moodley , Thadathilankal-Jess John , Sumanth Karamchand , Shivani Singh , Alfonso Pecararo , Anton Doubell , Charles Kyriakakis , Robin Warren , Leopoldo N. Segal , Grant Theron","doi":"10.1016/j.micinf.2024.105434","DOIUrl":"10.1016/j.micinf.2024.105434","url":null,"abstract":"<div><h3>Background</h3><div>The site-of-disease microbiome and predicted metagenome were evaluated in a cross-sectional study involving people with presumptive tuberculous pericarditis. We also explored the interaction between C-reactive protein (CRP) and the microbiome.</div></div><div><h3>Methods</h3><div>People with effusions requiring diagnostic pericardiocentesis (n=139) provided pericardial fluid for sequencing and blood for CRP measurement.</div></div><div><h3>Results</h3><div>Pericardial fluid microbiota differed in β-diversity among people with definite (dTB, n=91), probable (pTB, n=25), and non- (nTB, n=23) tuberculous pericarditis. dTBs were <em>Mycobacterium-, Lacticigenium-,</em> and <em>Kocuria-</em>enriched vs. nTBs. HIV-positive dTBs were <em>Mycobacterium-, Bifidobacterium-</em>, <em>Methylobacterium-</em>, and <em>Leptothrix</em>-enriched vs. HIV-negative dTBs. HIV-positive dTBs on ART were <em>Mycobacterium</em>- and <em>Bifidobacterium</em>-depleted vs. those not on ART. dTBs exhibited enrichment in short-chain fatty acid (SCFA) and mycobacterial metabolism pathways vs. nTBs. Additional non-pericardial involvement (pulmonary infiltrates) was associated with <em>Mycobacterium</em>-enrichment and <em>Streptococcus</em>-depletion. <em>Mycobacterium</em> reads were in 34 % (31/91) of dTBs, 8 % (2/25) of pTBs and 17 % (4/23) nTBs. People with CRP above (vs. below) the median value had different β-diversity (<em>Pseudomonas</em>-depleted). No correlation was found between enriched taxa in dTBs and CRP.</div></div><div><h3>Conclusions</h3><div>Pericardial fluid microbial composition varies by tuberculosis status, HIV (and ART) status and dTBs are enriched in SCFA-associated taxa. The clinical significance, including mycobacterial reads in nTBs and pTBs, requires evaluation.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 3","pages":"Article 105434"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142624005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The innate immune signals are the front line of host defense against bacterial pathogens. Pathogen-induced harmful effects, such as reduced neuronal signals to the intestine, affect the host's food sensing and dwelling behavior. Here, we report that dopamine and kpc-1 signals control the intestinal innate immune responses through the p38/PMK-1 MAPK signaling pathway in C. elegans. K. aerogenes infection in C. elegans affects the food-dwelling behavior, which depends on dopamine regulation. The absence of the dopamine receptor (dop-1) and transporter (dat-1) increases attraction to the pathogen instead of avoidance. The K. aerogenes infection affects age-1 regulation through the furin-like proprotein convertase (kpc-1); the absence of kpc-1 affects environment-dependent dauer formation. In contrast, the dop-1 mutation antagonistically regulates intestinal immune regulation, while the kpc-1 mutation partially regulates the p38/PMK-1 MAPK pathway. Our findings indicate that dopamine and kpc-1signaling from the nervous system control intestinal immunity in an antagonistic and agonistic manner, respectively.
{"title":"Dopaminergic neuronal regulation determines innate immunity of Caenorhabditis elegans during Klebsiella aerogenes infection","authors":"Gowripriya Thirumugam , Yashwanth Radhakrishnan , James Prabhanand Bhaskar , Suresh Ramamurthi , Balamurugan Krishnaswamy","doi":"10.1016/j.micinf.2024.105430","DOIUrl":"10.1016/j.micinf.2024.105430","url":null,"abstract":"<div><div>The innate immune signals are the front line of host defense against bacterial pathogens. Pathogen-induced harmful effects, such as reduced neuronal signals to the intestine, affect the host's food sensing and dwelling behavior. Here, we report that dopamine and <em>kpc-1</em> signals control the intestinal innate immune responses through the p38/PMK-1 MAPK signaling pathway in <em>C. elegans</em>. <em>K. aerogenes</em> infection in <em>C. elegans</em> affects the food-dwelling behavior, which depends on dopamine regulation. The absence of the dopamine receptor (<em>dop-1</em>) and transporter (<em>dat-1</em>) increases attraction to the pathogen instead of avoidance. The <em>K. aerogenes</em> infection affects <em>age-1</em> regulation through the furin-like proprotein convertase (<em>kpc-1</em>); the absence of <em>kpc-1</em> affects environment-dependent dauer formation. In contrast, the <em>dop-1</em> mutation antagonistically regulates intestinal immune regulation, while the <em>kpc-1</em> mutation partially regulates the p38/PMK-1 MAPK pathway. Our findings indicate that dopamine and <em>kpc-1</em>signaling from the nervous system control intestinal immunity in an antagonistic and agonistic manner, respectively.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 3","pages":"Article 105430"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142381261","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.micinf.2025.105477
Rabia Ladjouzi , Bernard Taminiau , Georges Daube , Anca Lucau-Danila , Djamel Drider
Purpose
To demonstrate the efficacy of the bacteriocinogenic Enterococcus faecalis 14 (E. faecalis 14) in the control of induced necrotic enteritis (NE) in broilers.
Methods
Six groups of 504 broilers consisting of an infected untreated control (IUC) group, an infected and amoxicillin treated control (ITC) group, and groups receiving prophylactically (2 groups) or therapeutically (2 groups) E. faecalis 14 or its Δbac mutant were used. All groups were challenged with Clostridium perfringens 56 to induce NE. To predispose the boilers to develop subclinical NE, a high protein grower diet containing 15 % fishmeal and a coccidial inoculum were administered.
Results
NE lesions were observed on D26 in all groups except ITC and those receiving prophylactically and therapeutically E. faecalis 14. On D27, only ITC and the group prophylactically treated with E. faecalis 14 (T03) were without lesions. Average body weight and daily weight gain remained lower in the treated groups compared to the ITC group, but there was a clear improvement in the period between D21 to D27, especially in the group prophylactically treated with E. faecalis 14. Specifically, the daily weight gain (DWG) in this period for group T03, was second highest after the group ITC. Metataxonomic analyses showed a positive effect of E. faecalis 14 in maintaining the diversity and richness of the intestinal microbiota, in contrast to ITC group and other conditions.
Conclusions
The results of this in vivo study demonstrated the efficacy of the prophylactic administration of the bacteriocinogenic E. faecalis 14 in preventing of the NE lesions caused by C. perfringens.
{"title":"The efficacy of the bacteriocinogenic Enterococcus faecalis 14 in the control of induced necrotic enteritis in broilers","authors":"Rabia Ladjouzi , Bernard Taminiau , Georges Daube , Anca Lucau-Danila , Djamel Drider","doi":"10.1016/j.micinf.2025.105477","DOIUrl":"10.1016/j.micinf.2025.105477","url":null,"abstract":"<div><h3>Purpose</h3><div>To demonstrate the efficacy of the bacteriocinogenic <em>Enterococcus faecalis</em> 14 (<em>E. faecalis</em> 14) in the control of induced necrotic enteritis (NE) in broilers.</div></div><div><h3>Methods</h3><div>Six groups of 504 broilers consisting of an infected untreated control (IUC) group, an infected and amoxicillin treated control (ITC) group, and groups receiving prophylactically (2 groups) or therapeutically (2 groups) <em>E. faecalis</em> 14 or its Δ<em>bac</em> mutant were used. All groups were challenged with <em>Clostridium perfringens</em> 56 to induce NE. To predispose the boilers to develop subclinical NE, a high protein grower diet containing 15 % fishmeal and a coccidial inoculum were administered.</div></div><div><h3>Results</h3><div>NE lesions were observed on D26 in all groups except ITC and those receiving prophylactically and therapeutically <em>E. faecalis</em> 14. On D27, only ITC and the group prophylactically treated with <em>E. faecalis</em> 14 (T03) were without lesions. Average body weight and daily weight gain remained lower in the treated groups compared to the ITC group, but there was a clear improvement in the period between D21 to D27, especially in the group prophylactically treated with <em>E. faecalis</em> 14. Specifically, the daily weight gain (DWG) in this period for group T03, was second highest after the group ITC. Metataxonomic analyses showed a positive effect of <em>E. faecalis</em> 14 in maintaining the diversity and richness of the intestinal microbiota, in contrast to ITC group and other conditions.</div></div><div><h3>Conclusions</h3><div>The results of this <em>in vivo</em> study demonstrated the efficacy of the prophylactic administration of the bacteriocinogenic <em>E. faecalis</em> 14 in preventing of the NE lesions caused by <em>C. perfringens</em>.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 3","pages":"Article 105477"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.micinf.2024.105438
Josephine E. Humphries , Steven D. Melvin , Chantal Lanctôt , Hamish McCallum , David Newell , Laura F. Grogan
The fungal disease chytridiomycosis (causative agent Batrachochytrium dendrobatidis [Bd]) is a primary contributor to amphibian species declines. The morphological and physiological reorganization that occurs during amphibian metamorphosis likely increases the vulnerability of metamorphs to Bd. To address this, we exposed pro-metamorphic tadpoles of Fleay's barred frog (Mixophyes fleayi) to Bd and sampled skin and liver sections from control and exposed animals throughout metamorphosis (Gosner stages 40, 42 and 45). We used an untargeted metabolomics approach to assess the metabolic impacts of Bd infection during the critical metamorphic stages, extracting metabolites from sampled tissues and analysing them via Nuclear Magnetic Resonance spectrometry. Most exposed animals became moribund at Gosner stage 45, while a subset seemingly cleared their infections. Metabolite abundance varied throughout development, with Gosner stage 45 samples distinct from previous stages. Clinically infected animals at Gosner stage 45 exhibited profound metabolic dysregulation (e.g., upregulation of amino acid biosynthesis and degradation) in comparison to uninfected groups (negative controls and ‘cleared’ animals). Despite showing parallels with previous metabolomic analyses of Bd-infected adult frogs, we identified variations in our results that could be attributed to the dramatic changes that characterise metamorphosis and may be driving the heightened vulnerability observed in metamorphic amphibians.
{"title":"Chytridiomycosis disrupts metabolic responses in amphibians at metamorphic climax","authors":"Josephine E. Humphries , Steven D. Melvin , Chantal Lanctôt , Hamish McCallum , David Newell , Laura F. Grogan","doi":"10.1016/j.micinf.2024.105438","DOIUrl":"10.1016/j.micinf.2024.105438","url":null,"abstract":"<div><div>The fungal disease chytridiomycosis (causative agent <em>Batrachochytrium dendrobatidis</em> [Bd]) is a primary contributor to amphibian species declines. The morphological and physiological reorganization that occurs during amphibian metamorphosis likely increases the vulnerability of metamorphs to Bd. To address this, we exposed pro-metamorphic tadpoles of Fleay's barred frog (<em>Mixophyes fleayi)</em> to Bd and sampled skin and liver sections from control and exposed animals throughout metamorphosis (Gosner stages 40, 42 and 45). We used an untargeted metabolomics approach to assess the metabolic impacts of Bd infection during the critical metamorphic stages, extracting metabolites from sampled tissues and analysing them via Nuclear Magnetic Resonance spectrometry. Most exposed animals became moribund at Gosner stage 45, while a subset seemingly cleared their infections. Metabolite abundance varied throughout development, with Gosner stage 45 samples distinct from previous stages. Clinically infected animals at Gosner stage 45 exhibited profound metabolic dysregulation (e.g., upregulation of amino acid biosynthesis and degradation) in comparison to uninfected groups (negative controls and ‘cleared’ animals). Despite showing parallels with previous metabolomic analyses of Bd-infected adult frogs, we identified variations in our results that could be attributed to the dramatic changes that characterise metamorphosis and may be driving the heightened vulnerability observed in metamorphic amphibians.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 3","pages":"Article 105438"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142648686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-03-01DOI: 10.1016/j.micinf.2024.105463
Shakyra Richardson , F.N.U. Medhavi , Tayhlor Tanner , Stephanie Lundy , Yusuf Omosun , Joseph U. Igietseme , Francis O. Eko
We investigated if the efficacy of a Chlamydia abortus (Cab) subunit vaccine is influenced by route of administration. Thus, female CBA/J mice were immunized either by mucosal or systemic routes with Vibrio cholerae ghost (VCG)-based vaccine expressing T and B cell epitopes of Cab polymorphic membrane protein (Pmp) 18D, termed rVCG-Pmp18.3. Vaccine evaluation revealed that all routes of vaccine delivery induced a Th1-type antibody response after a prime boost or three-dose immunization regimen. Also, the intranasal and rectal mucosal and intramuscular systemic routes induced cross-reactive neutralizing antibodies against homologous and heterologous Cab strains. Irrespective of the route of immunization, the vaccine elicited a Th1-type cytokine response (IFN-γ/IL-4 >1) in immunized mice. Analysis of reduction in genital Cab burden as an index of protection showed that immunization induced substantial degrees of protection against infection, irrespective of route of delivery with the intranasal and rectal mucosal routes showing superior levels of protection 12 days postchallenge. Furthermore, there was correlation between the humoral and cellular immune response and protection was associated with the Cab-specific serum IgG antibody avidity and IFN-γ. Thus, while route of administration impacts vaccine efficacy, the rVCG-Pmp18.3-induced protective immunity against Cab respiratory infection can be accomplished by both mucosal and systemic immunization.
{"title":"Role of route of delivery on Chlamydia abortus vaccine-induced immune responses and genital tract immunity in mice","authors":"Shakyra Richardson , F.N.U. Medhavi , Tayhlor Tanner , Stephanie Lundy , Yusuf Omosun , Joseph U. Igietseme , Francis O. Eko","doi":"10.1016/j.micinf.2024.105463","DOIUrl":"10.1016/j.micinf.2024.105463","url":null,"abstract":"<div><div>We investigated if the efficacy of a <em>Chlamydia abortus</em> (Cab) subunit vaccine is influenced by route of administration. Thus, female CBA/J mice were immunized either by mucosal or systemic routes with <em>Vibrio cholerae</em> ghost (VCG)-based vaccine expressing T and B cell epitopes of Cab polymorphic membrane protein (Pmp) 18D, termed rVCG-Pmp18.3. Vaccine evaluation revealed that all routes of vaccine delivery induced a Th1-type antibody response after a prime boost or three-dose immunization regimen. Also, the intranasal and rectal mucosal and intramuscular systemic routes induced cross-reactive neutralizing antibodies against homologous and heterologous Cab strains. Irrespective of the route of immunization, the vaccine elicited a Th1-type cytokine response (IFN-γ/IL-4 >1) in immunized mice. Analysis of reduction in genital Cab burden as an index of protection showed that immunization induced substantial degrees of protection against infection, irrespective of route of delivery with the intranasal and rectal mucosal routes showing superior levels of protection 12 days postchallenge. Furthermore, there was correlation between the humoral and cellular immune response and protection was associated with the Cab-specific serum IgG antibody avidity and IFN-γ. Thus, while route of administration impacts vaccine efficacy, the rVCG-Pmp18.3-induced protective immunity against Cab respiratory infection can be accomplished by both mucosal and systemic immunization.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 3","pages":"Article 105463"},"PeriodicalIF":2.6,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.micinf.2024.105407
Pingping Jia , Shize Peng , Yi Zhang , Jianyuan Zhao , Qianqian Zhao , Xiaoxiao Wu , Fangqi Shen , Kai Sun , Liyan Yu , Shan Cen
Tuberculosis (TB) is a high mortality infectious disease caused by Mycobacterium tuberculosis (Mtb), and often develops into latent infection. About 5～10% of latent infections turn into active tuberculosis when the host immune system becomes deficient. Therefore, exploring the latent infection mechanism of Mtb is pivotal for the prevention and treatment of tuberculosis. We first established the zebrafish latent infection model and the chronic infection model utilizing Mycobacterium marinum, which has the highly similar gene background to Mtb. Using the latent infection model, we characterized the gene expression profiles and found 462 genes expressed differentially in the latent period and chronic tuberculosis infection. These differentially expressed genes are involved in various biological processes including transcription, transcriptional regulation, organism development, and immune responses. Among them, nineteen immune-related genes were found to express differentially in the latent period. By analyzing immune related protein network, the genes in the center of the network, including Nos2b, TNFα, IL1, TNFβ, TLR1, TLR2, and TLR4b, displayed significant deferential expression in latent infection and chronic infection period of zebrafish, suggesting that these genes might play an important role in controlling latent infection of Mtb. Identifying immune biomarker related to the status of tuberculosis latent infection might lead to novel strategy for diagnosis and treatment.
{"title":"Identification of immune-associated genes involved in latent Mycobacterium marinum infection","authors":"Pingping Jia , Shize Peng , Yi Zhang , Jianyuan Zhao , Qianqian Zhao , Xiaoxiao Wu , Fangqi Shen , Kai Sun , Liyan Yu , Shan Cen","doi":"10.1016/j.micinf.2024.105407","DOIUrl":"10.1016/j.micinf.2024.105407","url":null,"abstract":"<div><div>Tuberculosis (TB) is a high mortality infectious disease caused by <em>Mycobacterium tuberculosis</em> (Mtb), and often develops into latent infection. About 5～10% of latent infections turn into active tuberculosis when the host immune system becomes deficient. Therefore, exploring the latent infection mechanism of Mtb is pivotal for the prevention and treatment of tuberculosis. We first established the zebrafish latent infection model and the chronic infection model utilizing <em>Mycobacterium marinum</em>, which has the highly similar gene background to Mtb. Using the latent infection model, we characterized the gene expression profiles and found 462 genes expressed differentially in the latent period and chronic tuberculosis infection. These differentially expressed genes are involved in various biological processes including transcription, transcriptional regulation, organism development, and immune responses. Among them, nineteen immune-related genes were found to express differentially in the latent period. By analyzing immune related protein network, the genes in the center of the network, including Nos2b, TNFα, IL1, TNFβ, TLR1, TLR2, and TLR4b, displayed significant deferential expression in latent infection and chronic infection period of zebrafish, suggesting that these genes might play an important role in controlling latent infection of Mtb. Identifying immune biomarker related to the status of tuberculosis latent infection might lead to novel strategy for diagnosis and treatment.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 2","pages":"Article 105407"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046883","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Currently, fungal and bacterial skin infections rank among the most challenging public health problems due to the increasing prevalence of microorganisms and the development of resistance to available drugs. A major issue in treating these infections with conventional topical medications is the poor penetration through the stratum corneum, the outermost layer of the skin. The concept of microneedles seems to be a future-proof approach for delivering drugs directly into deeper tissues. By bypassing the skin barrier, microneedle systems allow therapeutic substances to reach deeper layers more efficiently, significantly improving treatment outcomes. Nonetheless, the primary challenges regarding the effectiveness of microneedles involve selecting the appropriate size and shape, along with polymer composition and fabrication technology, to enable controlled and efficient drug release. This review offers a comprehensive overview of the latest knowledge on microneedle types and manufacturing techniques, highlighting their potential effectiveness in treating bacterial and fungal skin infections. It includes updated statistics on infection prevalence and provides a detailed examination of common bacterial and fungal diseases, focusing on their symptoms, causative species, and treatment methods. Additionally, the review addresses safety considerations, regulatory aspects, and future perspectives for microneedle-based therapeutic systems. It also underscores the importance of industrialization and clinical translation efforts, emphasizing the significant potential of microneedle technology for advancing medical applications.
{"title":"Microneedle-based arrays – Breakthrough strategy for the treatment of bacterial and fungal skin infections","authors":"Oliwia Kordyl , Zuzanna Styrna , Monika Wojtyłko , Bozena Michniak-Kohn , Tomasz Osmałek","doi":"10.1016/j.micinf.2024.105426","DOIUrl":"10.1016/j.micinf.2024.105426","url":null,"abstract":"<div><div>Currently, fungal and bacterial skin infections rank among the most challenging public health problems due to the increasing prevalence of microorganisms and the development of resistance to available drugs. A major issue in treating these infections with conventional topical medications is the poor penetration through the <em>stratum corneum</em>, the outermost layer of the skin. The concept of microneedles seems to be a future-proof approach for delivering drugs directly into deeper tissues. By bypassing the skin barrier, microneedle systems allow therapeutic substances to reach deeper layers more efficiently, significantly improving treatment outcomes. Nonetheless, the primary challenges regarding the effectiveness of microneedles involve selecting the appropriate size and shape, along with polymer composition and fabrication technology, to enable controlled and efficient drug release. This review offers a comprehensive overview of the latest knowledge on microneedle types and manufacturing techniques, highlighting their potential effectiveness in treating bacterial and fungal skin infections. It includes updated statistics on infection prevalence and provides a detailed examination of common bacterial and fungal diseases, focusing on their symptoms, causative species, and treatment methods. Additionally, the review addresses safety considerations, regulatory aspects, and future perspectives for microneedle-based therapeutic systems. It also underscores the importance of industrialization and clinical translation efforts, emphasizing the significant potential of microneedle technology for advancing medical applications.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 2","pages":"Article 105426"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142349788","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.micinf.2024.105420
Jelena Repac, Bojan Božić, Biljana Božić Nedeljković
Cutibacterium acnes, common resident of the human skin, can establish both commensal and pathogenic relations with the human host; however, long-term consequences of C. acnes-induced inflammation remained un(der)explored. To infer the capacity of triggering autoimmunity in humans via molecular mimicry, a comprehensive immunoinformatics analysis of the experimentally characterized C. acnes proteome was performed. The protocol included homology screening between the C. acnes and the human proteome, and validation of shared specificity regions against the collection of experimentally characterized T-cell epitopes, related to autoimmunity. To obtain highly reliable predictions, the results were subjected to additional cross-validation by a dedicated MHC-restriction analysis, including a docking study of C. acnes mimotopes and human counterparts with the highest degree of sequence similarity to MHCII molecules representing the highest risk for detected autoimmune pathologies. Due to mimicking of highly immunogenic, but also evolutionary conserved autoantigens from the Heat Shock protein family, association between C. acnes and the pathogenesis of highly incident autoimmune diseases: Type 1 Diabetes, Rheumatoid Arthritis, and Juvenile Idiopathic Arthritis, was found. To the best of our knowledge, this study is the first one to provide preliminary information and a mechanistic link on the putative involvement of C. acnes in the pathogenesis of autoimmunity in humans.
痤疮丙酸杆菌是人类皮肤的常见寄生菌，可与人类宿主建立共生和致病关系；然而，痤疮丙酸杆菌诱发炎症的长期后果仍有待探索。为了推断痤疮丙酸杆菌通过分子模仿引发人类自身免疫的能力，我们对实验表征的痤疮丙酸杆菌蛋白质组进行了全面的免疫信息学分析。该方案包括痤疮丙酸杆菌与人类蛋白质组之间的同源性筛选，以及针对实验表征的与自身免疫相关的 T 细胞表位集合对共享特异性区域的验证。为了获得高度可靠的预测结果，还通过专门的 MHC 限制分析对结果进行了交叉验证，包括痤疮丙酸杆菌模拟物与人类对应物的对接研究，这些模拟物与 MHCII 分子的序列相似度最高，代表了检测到的自身免疫性病症的最高风险。由于痤疮丙酸杆菌模仿了热休克蛋白家族中高免疫原性但也是进化保守的自身抗原，因此痤疮丙酸杆菌与高发自身免疫性疾病的发病机制存在关联：我们发现痤疮丙酸杆菌与高发自身免疫性疾病（1 型糖尿病、类风湿关节炎和幼年特发性关节炎）的发病机制存在关联。据我们所知，这项研究首次提供了痤疮丙酸杆菌可能参与人类自身免疫性疾病发病机制的初步信息和机制联系。
{"title":"Cutibacterium acnes as an overseen autoimmunity trigger: Unearthing heat-shock driven molecular mimicry","authors":"Jelena Repac, Bojan Božić, Biljana Božić Nedeljković","doi":"10.1016/j.micinf.2024.105420","DOIUrl":"10.1016/j.micinf.2024.105420","url":null,"abstract":"<div><div><em>Cutibacterium acnes</em>, common resident of the human skin, can establish both commensal and pathogenic relations with the human host; however, long-term consequences of <em>C. acnes-</em>induced inflammation remained un(der)explored. To infer the capacity of triggering autoimmunity in humans <em>via</em> molecular mimicry, a comprehensive immunoinformatics analysis of the experimentally characterized <em>C. acnes</em> proteome was performed. The protocol included homology screening between the <em>C. acnes</em> and the human proteome, and validation of shared specificity regions against the collection of experimentally characterized T-cell epitopes, related to autoimmunity. To obtain highly reliable predictions, the results were subjected to additional cross-validation by a dedicated MHC-restriction analysis, including a docking study of <em>C. acnes</em> mimotopes and human counterparts with the highest degree of sequence similarity to MHCII molecules representing the highest risk for detected autoimmune pathologies. Due to mimicking of highly immunogenic, but also evolutionary conserved autoantigens from the Heat Shock protein family, association between <em>C. acnes</em> and the pathogenesis of highly incident autoimmune diseases: Type 1 Diabetes, Rheumatoid Arthritis, and Juvenile Idiopathic Arthritis, was found. To the best of our knowledge, this study is the first one to provide preliminary information and a mechanistic link on the putative involvement of <em>C. acnes</em> in the pathogenesis of autoimmunity in humans.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 2","pages":"Article 105420"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142154543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.micinf.2024.105411
Andrea Borrego , Wafa Hanna Koury Cabrera , Alanis Tiozzo Souza , Silas Fernandes Eto , Silvio Luis de Oliveira , Josias Rodrigues , José Ricardo Jensen
Genetics is central to the susceptibility or resistance to autoimmunity, and mounting evidence indicates that the intestinal microbiota also plays an essential role. In murine arthritis models, short-chain fat acid supplementation reduces disease severity by modulating tryptophan-metabolizing bacteria. Common microbiota transfer methods modulate arthritis severity, however, they are not practical for chronic models such as pristane-induced arthritis (PIA). PIA-resistant (HIII) and PIA-susceptible (LIII) mice harbor diverse intestinal microbiomes, which might be implicated in their divergent susceptibility. To investigate this hypothesis, we used cross-fostering to stably transfer the microbiota. In this study, we show that extreme susceptibility to arthritis can be modulated by early microbiota transfer, with long-lasting effects. HIII and LIII pups were cross-fostered and injected with pristane after weaning. PIA severity in cross-fostered LIII mice was significantly reduced in the chronic phase. Metagenomic analyses showed that HIII and LIII microbiomes were partly shifted by cross-fostering. Microbial groups whose abundance was associated with either HIII or LIII mice presented similar composition in cross-fostered mice of the opposite strains, suggesting a role in PIA susceptibility. Identification of bacterial groups that modulate chronic arthritis will contribute novel insights on the pathogenesis of human rheumatoid arthritis and targets for replication and functional studies.
遗传是自身免疫易感性或抵抗力的核心，越来越多的证据表明，肠道微生物群也起着至关重要的作用。在小鼠关节炎模型中，补充短链脂肪酸可通过调节色氨酸代谢细菌来减轻疾病的严重程度。常见的微生物群转移方法可以调节关节炎的严重程度，但对于慢性模型，如普里斯坦诱导的关节炎（PIA），这些方法并不实用。PIA耐药小鼠（HIII）和PIA易感小鼠（LIII）拥有不同的肠道微生物群，这可能与它们不同的易感性有关。为了研究这一假说，我们采用了交叉培养的方法来稳定转移微生物群。在这项研究中，我们发现对关节炎的极端易感性可以通过早期微生物群转移来调节，并产生持久的影响。对HIII和LIII幼鼠进行交叉寄养，并在断奶后注射普利斯坦。交叉寄养的 LIII 小鼠在慢性阶段的 PIA 严重程度明显降低。元基因组分析表明，HIII 和 LIII 微生物组因交叉寄养而发生了部分变化。与HIII或LIII小鼠丰度相关的微生物群在相反品系的交叉寄养小鼠中呈现出相似的组成，这表明它们在PIA易感性中发挥了作用。鉴定调节慢性关节炎的细菌群将有助于深入了解人类类风湿性关节炎的发病机制，并为复制和功能研究提供目标。
{"title":"Microbiota transfer early after birth modulates genetic susceptibility to chronic arthritis in mice","authors":"Andrea Borrego , Wafa Hanna Koury Cabrera , Alanis Tiozzo Souza , Silas Fernandes Eto , Silvio Luis de Oliveira , Josias Rodrigues , José Ricardo Jensen","doi":"10.1016/j.micinf.2024.105411","DOIUrl":"10.1016/j.micinf.2024.105411","url":null,"abstract":"<div><div>Genetics is central to the susceptibility or resistance to autoimmunity, and mounting evidence indicates that the intestinal microbiota also plays an essential role. In murine arthritis models, short-chain fat acid supplementation reduces disease severity by modulating tryptophan-metabolizing bacteria. Common microbiota transfer methods modulate arthritis severity, however, they are not practical for chronic models such as pristane-induced arthritis (PIA). PIA-resistant (HIII) and PIA-susceptible (LIII) mice harbor diverse intestinal microbiomes, which might be implicated in their divergent susceptibility. To investigate this hypothesis, we used cross-fostering to stably transfer the microbiota. In this study, we show that extreme susceptibility to arthritis can be modulated by early microbiota transfer, with long-lasting effects. HIII and LIII pups were cross-fostered and injected with pristane after weaning. PIA severity in cross-fostered LIII mice was significantly reduced in the chronic phase. Metagenomic analyses showed that HIII and LIII microbiomes were partly shifted by cross-fostering. Microbial groups whose abundance was associated with either HIII or LIII mice presented similar composition in cross-fostered mice of the opposite strains, suggesting a role in PIA susceptibility. Identification of bacterial groups that modulate chronic arthritis will contribute novel insights on the pathogenesis of human rheumatoid arthritis and targets for replication and functional studies.</div></div>","PeriodicalId":18497,"journal":{"name":"Microbes and Infection","volume":"27 2","pages":"Article 105411"},"PeriodicalIF":2.6,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142109246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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