Pub Date : 2022-11-01Epub Date: 2022-09-06DOI: 10.1111/pim.12945
Heba H Bakery, Gamal A Allam, Abdelaziz S A Abuelsaad, Mahmoud Abdel-Latif, Ayman E Elkenawy, Rehab G Khalil
Schistosomiasis is still a major health problem affecting nearly 250 million people worldwide and causes approximately 280,000 deaths per year. The disease causes a serious granulomatous inflammatory response that produces significant mortality. Plumbagin reportedly displays anti-inflammatory, anti-fibrotic, antioxidant and anthelmintic properties. This study further elucidates these properties. Mice were infected with schistosomes and divided into five groups: non-infected untreated (C); infected untreated (IU); non-infected treated with plumbagin (P); infected treated with plumbagin (PI) and infected treated with praziquantel (PZ). Mice treated with 20 mg plumbagin/kg body weight showed reduction of 64.28% and 59.88% in male and female animals, respectively. Also, the number of eggs/g tissue was reduced 69.39%, 68.79% and 69.11% in liver, intestine and liver/intestine combined, respectively. Plumbagin alleviated schistosome-induced hepatosplenomegaly and reduced hepatic granuloma and liver collagen content by 62.5% and 35.26%, respectively while PZQ reduced hepatic granuloma and liver collagen content by 41.11% and 11.21%, respectively. Further, plumbagin treatment significantly (p < .001) reduced IL-4, IL-13, IL-17, IL-37, IFN-γ, TGF-β and TNF-α levels and significantly (p < .001) upregulated IL-10. Plumbagin treatment restored hepatic enzymes activity to nearly normal levels and induced an increase in catalase, SOD, GSH, total thiol and GST in liver tissue homogenate. NO and LPO content was, however, decreased. Moreover, serum IgG levels significantly increased. The present study is the first to report immunomodulatory and schistosomicidal activities of plumbagin in schistosomiasis.
{"title":"Anti-inflammatory, antioxidant, anti-fibrotic and schistosomicidal properties of plumbagin in murine schistosomiasis.","authors":"Heba H Bakery, Gamal A Allam, Abdelaziz S A Abuelsaad, Mahmoud Abdel-Latif, Ayman E Elkenawy, Rehab G Khalil","doi":"10.1111/pim.12945","DOIUrl":"https://doi.org/10.1111/pim.12945","url":null,"abstract":"<p><p>Schistosomiasis is still a major health problem affecting nearly 250 million people worldwide and causes approximately 280,000 deaths per year. The disease causes a serious granulomatous inflammatory response that produces significant mortality. Plumbagin reportedly displays anti-inflammatory, anti-fibrotic, antioxidant and anthelmintic properties. This study further elucidates these properties. Mice were infected with schistosomes and divided into five groups: non-infected untreated (C); infected untreated (IU); non-infected treated with plumbagin (P); infected treated with plumbagin (PI) and infected treated with praziquantel (PZ). Mice treated with 20 mg plumbagin/kg body weight showed reduction of 64.28% and 59.88% in male and female animals, respectively. Also, the number of eggs/g tissue was reduced 69.39%, 68.79% and 69.11% in liver, intestine and liver/intestine combined, respectively. Plumbagin alleviated schistosome-induced hepatosplenomegaly and reduced hepatic granuloma and liver collagen content by 62.5% and 35.26%, respectively while PZQ reduced hepatic granuloma and liver collagen content by 41.11% and 11.21%, respectively. Further, plumbagin treatment significantly (p < .001) reduced IL-4, IL-13, IL-17, IL-37, IFN-γ, TGF-β and TNF-α levels and significantly (p < .001) upregulated IL-10. Plumbagin treatment restored hepatic enzymes activity to nearly normal levels and induced an increase in catalase, SOD, GSH, total thiol and GST in liver tissue homogenate. NO and LPO content was, however, decreased. Moreover, serum IgG levels significantly increased. The present study is the first to report immunomodulatory and schistosomicidal activities of plumbagin in schistosomiasis.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40352430","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}
Experimental autoimmune encephalomyelitis (EAE) is an appropriate model for the study of the immunologic and pathologic mechanisms in multiple sclerosis (MS). According to the hygiene hypothesis, helminths can improve immunoregulation and have therapeutic effects on immune-mediated diseases. In this study, we used Dicrocoelium dendriticum (Dicrocoeliidae, Platyhelminthes) eggs for the evaluation of their prophylactic and treatment effects on EAE disease. D. dendriticum eggs were extracted. Female C57BL/6 mice were immunized with the specific antigen MOG35-55 , and then the egg extracts were utilized for prophylaxis and/or treatment. Clinical symptoms and other relevant parameters were assessed daily. The mRNA expression of transforming growth factor-β (TGF-β), interleukin-10 (IL-10), IL-6, IL-23 and IL-17 were assessed with a real-time polymerase chain reaction technique. Furthermore, secretion of TGF-β and IL-17 cytokines were determined by enzyme-linked immunosorbent assay. Data indicated that clinical symptoms in prophylaxis and treatment groups were decreased significantly in comparison with the untreated control group (p < .001). Our results showed a significant decrease in IL-17, as well as an increase in TGF-β cytokine in the treatment group compared to the EAE control group (p < .01). Furthermore, in the prophylaxis and treatment groups, the mRNA expression of disease-associated cytokines decreased and the mRNA expression of the anti-inflammatory cytokines increased. In this study, the D. dendriticum egg ameliorates the clinical symptoms of the EAE model through the modulation of related cytokines of Th17 and Treg cells. Therefore, using this parasite egg could be a new treatment for MS.
{"title":"Evaluation of the immunoregulatory effect of Dicrocoelium dendriticum eggs on inflammatory and anti-inflammatory cytokines in EAE model.","authors":"Mozhdeh Jafari Rad, Zahra Navi, Amir Reza Heidari, Fahimeh Lavi Arab, Nafiseh Tabasi, Maryam Rastin, Majid Khadem Rezaiyan, Elham Moghaddas, Mahmoud Mahmoudi","doi":"10.1111/pim.12942","DOIUrl":"https://doi.org/10.1111/pim.12942","url":null,"abstract":"<p><p>Experimental autoimmune encephalomyelitis (EAE) is an appropriate model for the study of the immunologic and pathologic mechanisms in multiple sclerosis (MS). According to the hygiene hypothesis, helminths can improve immunoregulation and have therapeutic effects on immune-mediated diseases. In this study, we used Dicrocoelium dendriticum (Dicrocoeliidae, Platyhelminthes) eggs for the evaluation of their prophylactic and treatment effects on EAE disease. D. dendriticum eggs were extracted. Female C57BL/6 mice were immunized with the specific antigen MOG<sub>35-55</sub> , and then the egg extracts were utilized for prophylaxis and/or treatment. Clinical symptoms and other relevant parameters were assessed daily. The mRNA expression of transforming growth factor-β (TGF-β), interleukin-10 (IL-10), IL-6, IL-23 and IL-17 were assessed with a real-time polymerase chain reaction technique. Furthermore, secretion of TGF-β and IL-17 cytokines were determined by enzyme-linked immunosorbent assay. Data indicated that clinical symptoms in prophylaxis and treatment groups were decreased significantly in comparison with the untreated control group (p < .001). Our results showed a significant decrease in IL-17, as well as an increase in TGF-β cytokine in the treatment group compared to the EAE control group (p < .01). Furthermore, in the prophylaxis and treatment groups, the mRNA expression of disease-associated cytokines decreased and the mRNA expression of the anti-inflammatory cytokines increased. In this study, the D. dendriticum egg ameliorates the clinical symptoms of the EAE model through the modulation of related cytokines of Th17 and Treg cells. Therefore, using this parasite egg could be a new treatment for MS.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40344277","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}
Cystic echinococcosis (CE) is one of the most important zoonotic diseases with a worldwide distribution. It is caused by the larval stage of the dog tapeworm "Echinococcus granulosussensu lato" and constitutes a major economic and public health problem in several countries. Protoscoleces are one component of this larval stage that can interact with both definitive and intermediate hosts. The aim of the present study was to investigate the potential role of using a radio-attenuated form of these protoscoleces for immunoprophylaxis against experimental murine echinococcosis. However, mice were immunized twice at 15-day intervals with gamma (γ) irradiated protoscoleces at doses of 0.4, 0.8, 1.2 and 1.4 kGy then challenged with the intact parasites. Macroscopic and histological analyses with cytokine measurements were performed in order to estimate the number and diameter of cysts, microscopic changes and cytokine profile. An improvement in protection against the challenge dose was observed with increasing dose, giving percentages of 47.7, 49, 55.23 and 70.6%, for the 0.4, 0.8, 1.2 and 1.4 kGy-groups respectively. These data suggest that immunization with radio-attenuated protoscoleces may induce satisfactory protective immunity by reducing successfully the formation of cysts, caused by challenge infection.
{"title":"Treatment of protoscoleces with gamma radiation: Potential immunoprotective effect against experimental murine echinococcosis.","authors":"Samia Hadj Rabia, Aicha Debib, Meriem Mezaguer, Rabah Yefsah, Imene Soufli, Bousaad Hamrioui, Chafia Touil-Boukoffa, Ahsene Baz, Jean Giaimis, Saâdia Mameri","doi":"10.1111/pim.12944","DOIUrl":"https://doi.org/10.1111/pim.12944","url":null,"abstract":"<p><p>Cystic echinococcosis (CE) is one of the most important zoonotic diseases with a worldwide distribution. It is caused by the larval stage of the dog tapeworm \"Echinococcus granulosussensu lato\" and constitutes a major economic and public health problem in several countries. Protoscoleces are one component of this larval stage that can interact with both definitive and intermediate hosts. The aim of the present study was to investigate the potential role of using a radio-attenuated form of these protoscoleces for immunoprophylaxis against experimental murine echinococcosis. However, mice were immunized twice at 15-day intervals with gamma (γ) irradiated protoscoleces at doses of 0.4, 0.8, 1.2 and 1.4 kGy then challenged with the intact parasites. Macroscopic and histological analyses with cytokine measurements were performed in order to estimate the number and diameter of cysts, microscopic changes and cytokine profile. An improvement in protection against the challenge dose was observed with increasing dose, giving percentages of 47.7, 49, 55.23 and 70.6%, for the 0.4, 0.8, 1.2 and 1.4 kGy-groups respectively. These data suggest that immunization with radio-attenuated protoscoleces may induce satisfactory protective immunity by reducing successfully the formation of cysts, caused by challenge infection.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40345218","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 : 2022-10-01Epub Date: 2022-08-02DOI: 10.1111/pim.12941
Ashley E Steuer, Kirsten Scoggin, John C Stewart, Virginia D Barker, Amanda A Adams, Alan T Loynachan, Martin K Nielsen
This study aimed to collect information on local and systemic inflammatory responses, and goblet cell-associated components, following anthelmintic treatment with moxidectin and ivermectin in horses naturally infected with cyathostomin parasites. Thirty-six horses aged 2-5 years of age were randomly allocated to three groups. Group 1 received ivermectin/praziquantel (0.2 mg/kg), Group 2 received moxidectin/praziquantel (0.4 mg/kg) and Group 3 were untreated controls. Tissue samples from the Cecum, Dorsal and Ventral Colons were used for histopathological evaluation and preserved for RNA isolation and gene expression analysis. Whole blood was collected weekly for gene expression analysis as well. The control group had significantly higher inflammation associated with higher larval scores. The treatment groups displayed no differences in larval counts and inflammatory cell populations (p > .05). Mucosal larval counts were positively correlated with goblet cell hyperplasia scores (p = .047). The moxidectin-treated group had a significantly lower expression of IFN-γ (p < .05). The data suggest that removal of cyathostomins reduced the pro-inflammatory response associated with cyathostomin infections. Pro-inflammatory reactions associated with anthelmintic treatment were minimal, but lowest for moxidectin-treated horses. Results suggested that cecum, ventral and dorsal colons responded differently to cyathostomin larvae, which may have implications in the disease process.
{"title":"Comparison of the host response to larvicidal and nonlarvicidal treatment of naturally acquired cyathostomin infections in horses.","authors":"Ashley E Steuer, Kirsten Scoggin, John C Stewart, Virginia D Barker, Amanda A Adams, Alan T Loynachan, Martin K Nielsen","doi":"10.1111/pim.12941","DOIUrl":"https://doi.org/10.1111/pim.12941","url":null,"abstract":"<p><p>This study aimed to collect information on local and systemic inflammatory responses, and goblet cell-associated components, following anthelmintic treatment with moxidectin and ivermectin in horses naturally infected with cyathostomin parasites. Thirty-six horses aged 2-5 years of age were randomly allocated to three groups. Group 1 received ivermectin/praziquantel (0.2 mg/kg), Group 2 received moxidectin/praziquantel (0.4 mg/kg) and Group 3 were untreated controls. Tissue samples from the Cecum, Dorsal and Ventral Colons were used for histopathological evaluation and preserved for RNA isolation and gene expression analysis. Whole blood was collected weekly for gene expression analysis as well. The control group had significantly higher inflammation associated with higher larval scores. The treatment groups displayed no differences in larval counts and inflammatory cell populations (p > .05). Mucosal larval counts were positively correlated with goblet cell hyperplasia scores (p = .047). The moxidectin-treated group had a significantly lower expression of IFN-γ (p < .05). The data suggest that removal of cyathostomins reduced the pro-inflammatory response associated with cyathostomin infections. Pro-inflammatory reactions associated with anthelmintic treatment were minimal, but lowest for moxidectin-treated horses. Results suggested that cecum, ventral and dorsal colons responded differently to cyathostomin larvae, which may have implications in the disease process.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2022-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40528311","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}
Leishmaniasis includes several clinical forms. While routine diagnosis of cutaneous leishmaniasis (CL) is by microscopy, an antibody response to CL has been reported in several recent studies. This study evaluated anti-leishmanial immunoglobulin G (IgG) antibody responses as a biomarker of active leishmaniasis and a measure of exposure to Leishmania. Sera from 50 untreated CL patients, 140 patients under treatment and 280 healthy individuals residing in endemic regions collected as part of an epidemiological survey, was analysed with an enzyme-linked immunosorbent assay established in-house using receiver operator characteristic curve at optimized cut-off value. The assay showed high performance as a diagnostic tool in identifying exposure in endemic individuals (sensitivity: 98%, specificity: 90.3%). All patients showed lower antibody levels over time since onset of lesion/s. Antibody levels were higher (p ˂ .01) and persisted for a longer period in untreated patients. In patients under treatment, the level of anti-IgG antibodies was negatively correlated with the total duration the patient had been on treatment. The anti-leishmanial IgG response in Leishmania donovani-induced CL is transient and is unlikely to confer protective immunity. Optimized serological assays may be useful in endemic settings for diagnosis and monitoring the treatment response in CL.
{"title":"ELISA-based evaluation of antibody response to Leishmania in a region endemic for cutaneous leishmaniasis.","authors":"Sachee Bhanu Piyasiri, Thisum Nilakshi Samaranayake, Hermali Silva, Nuwani Harshamali Manamperi, Nadira Darshani Karunaweera","doi":"10.1111/pim.12940","DOIUrl":"https://doi.org/10.1111/pim.12940","url":null,"abstract":"<p><p>Leishmaniasis includes several clinical forms. While routine diagnosis of cutaneous leishmaniasis (CL) is by microscopy, an antibody response to CL has been reported in several recent studies. This study evaluated anti-leishmanial immunoglobulin G (IgG) antibody responses as a biomarker of active leishmaniasis and a measure of exposure to Leishmania. Sera from 50 untreated CL patients, 140 patients under treatment and 280 healthy individuals residing in endemic regions collected as part of an epidemiological survey, was analysed with an enzyme-linked immunosorbent assay established in-house using receiver operator characteristic curve at optimized cut-off value. The assay showed high performance as a diagnostic tool in identifying exposure in endemic individuals (sensitivity: 98%, specificity: 90.3%). All patients showed lower antibody levels over time since onset of lesion/s. Antibody levels were higher (p ˂ .01) and persisted for a longer period in untreated patients. In patients under treatment, the level of anti-IgG antibodies was negatively correlated with the total duration the patient had been on treatment. The anti-leishmanial IgG response in Leishmania donovani-induced CL is transient and is unlikely to confer protective immunity. Optimized serological assays may be useful in endemic settings for diagnosis and monitoring the treatment response in CL.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9481270/pdf/nihms-1823708.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10135275","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 : 2022-09-01Epub Date: 2022-07-05DOI: 10.1111/pim.12939
Agnes Natukunda, Ludoviko Zirimenya, Jacent Nassuuna, Gyaviira Nkurunungi, Stephen Cose, Alison M Elliott, Emily L Webb
Vaccination has potential to eliminate infectious diseases. However, parasitic infections such as helminths may hinder vaccines from providing optimal protection. We reviewed existing literature on the effects of helminth infections and their treatment on vaccine responses in humans and animals. We searched literature until 31 January 2022 in Medline, EMBASE, Global health, Scopus, and Web of science; search terms included WHO licensed vaccines and human helminth types. Standardized mean differences (SMD) in vaccine responses between helminth infected and uninfected or anthelminthic treated and untreated individuals were obtained from each study with suitable data for meta-analysis, and combined using a random effects model. Analysis was stratified by whether helminth exposure was direct or prenatal and by vaccine type. This study is registered with PROSPERO (CRD42019123074). Of the 4402 articles identified, 37 were included in the review of human studies and 24 for animal experiments. For human studies, regardless of vaccine type, overall SMD for helminth uninfected/treated, compared to infected/untreated, was 0.56 (95% CI 0.04-1.07 and I2 = 93.5%) for direct helminth exposure and 0.01 (95% CI -0.04 to 0.07 and I2 = 85.9%) for prenatal helminth exposure. Effects of anthelminthic treatment were inconsistent, with no overall benefit shown. Results differed by vaccine type, with responses to live vaccines most affected by helminth exposure. For animal studies, the most affected vaccine was BCG. This result indicates that helminth-associated impairment of vaccine responses is more severe for direct, than for prenatal, helminth exposure. Further research is needed to ascertain whether deworming of individuals before vaccination may help improve responses.
{"title":"The effect of helminth infection on vaccine responses in humans and animal models: A systematic review and meta-analysis.","authors":"Agnes Natukunda, Ludoviko Zirimenya, Jacent Nassuuna, Gyaviira Nkurunungi, Stephen Cose, Alison M Elliott, Emily L Webb","doi":"10.1111/pim.12939","DOIUrl":"10.1111/pim.12939","url":null,"abstract":"<p><p>Vaccination has potential to eliminate infectious diseases. However, parasitic infections such as helminths may hinder vaccines from providing optimal protection. We reviewed existing literature on the effects of helminth infections and their treatment on vaccine responses in humans and animals. We searched literature until 31 January 2022 in Medline, EMBASE, Global health, Scopus, and Web of science; search terms included WHO licensed vaccines and human helminth types. Standardized mean differences (SMD) in vaccine responses between helminth infected and uninfected or anthelminthic treated and untreated individuals were obtained from each study with suitable data for meta-analysis, and combined using a random effects model. Analysis was stratified by whether helminth exposure was direct or prenatal and by vaccine type. This study is registered with PROSPERO (CRD42019123074). Of the 4402 articles identified, 37 were included in the review of human studies and 24 for animal experiments. For human studies, regardless of vaccine type, overall SMD for helminth uninfected/treated, compared to infected/untreated, was 0.56 (95% CI 0.04-1.07 and I<sup>2</sup> = 93.5%) for direct helminth exposure and 0.01 (95% CI -0.04 to 0.07 and I<sup>2</sup> = 85.9%) for prenatal helminth exposure. Effects of anthelminthic treatment were inconsistent, with no overall benefit shown. Results differed by vaccine type, with responses to live vaccines most affected by helminth exposure. For animal studies, the most affected vaccine was BCG. This result indicates that helminth-associated impairment of vaccine responses is more severe for direct, than for prenatal, helminth exposure. Further research is needed to ascertain whether deworming of individuals before vaccination may help improve responses.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2022-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9542036/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9157720","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 : 2022-08-01Epub Date: 2022-05-31DOI: 10.1111/pim.12936
Stefano A P Colombo, Seona Thompson, Allison J Bancroft, Richard K Grencis
In endemic regions concurrent infection with multiple gastrointestinal (GI) helminth species is more common than single species infection. However, the majority of model helminth infections focus on single species infections leading to a lack of understanding of how co-infection influences anti-parasite immune responses. Here, we use a model co-infection of Trichuris muris (Tm) and Heligmosomoides bakeri (Hb) to investigate the effect of Hb on anti-Tm immune responses. We observed a complete impairment of Tm expulsion in immune competent C57BL/6 mice when co-infected with Hb. This was coupled with reduced cellularity in the colonic mesenteric lymph node (cMLN) proximal to the caecum, however, cMLN cytokine responses and caecal mucosal immune responses in co-infected mice were not significantly different from mice infected with Tm alone. Interestingly, in immune-compromised mice, we found co-infection resulted in enhanced growth and fecundity of female Tm parasites. These data suggest that during helminth-helminth co-infection, immune-independent signals between species may promote survival and growth.
{"title":"Anti-Trichuris mucosal responses are maintained during H. bakeri co-infection despite impaired parasite expulsion.","authors":"Stefano A P Colombo, Seona Thompson, Allison J Bancroft, Richard K Grencis","doi":"10.1111/pim.12936","DOIUrl":"10.1111/pim.12936","url":null,"abstract":"<p><p>In endemic regions concurrent infection with multiple gastrointestinal (GI) helminth species is more common than single species infection. However, the majority of model helminth infections focus on single species infections leading to a lack of understanding of how co-infection influences anti-parasite immune responses. Here, we use a model co-infection of Trichuris muris (Tm) and Heligmosomoides bakeri (Hb) to investigate the effect of Hb on anti-Tm immune responses. We observed a complete impairment of Tm expulsion in immune competent C57BL/6 mice when co-infected with Hb. This was coupled with reduced cellularity in the colonic mesenteric lymph node (cMLN) proximal to the caecum, however, cMLN cytokine responses and caecal mucosal immune responses in co-infected mice were not significantly different from mice infected with Tm alone. Interestingly, in immune-compromised mice, we found co-infection resulted in enhanced growth and fecundity of female Tm parasites. These data suggest that during helminth-helminth co-infection, immune-independent signals between species may promote survival and growth.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2022-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9542692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90753147","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}
The chemokine receptor CCR7 is a well‐established homing receptor for dendritic cells (DCs) and T‐cells. Interaction with the CCL19 and CCL21 ligands promotes priming of immune responses in lymphoid tissues; however, the mechanism underlying CCR7‐induced immune responses against helminth parasite infection remains unknown. Thus, we examined the role of CCR7 in generating protective immune responses against intracellular Trichinella spiralis infection. The results showed significantly increased CCR7, CCL19 and CCL21 expression in the muscle tissue compared to that in the intestinal tissue in T. spiralis‐infected mice. The CCR7‐expressing DC population increased in the mesenteric and peripheral lymph nodes (PLNs) during T. spiralis infection. Notably, the number of CCR7‐expressing cells in PLNs increased by more than 30% at 28 days post‐infection; however, this increase was significantly inhibited in CCR7‐blocked mice treated with CCR7‐specific antibodies. T helper 2 (Th2)‐and regulatory T (Treg)‐related cytokine levels were also reduced by CCR7‐specific antibody treatment. CCR7‐blocked mice lost their resistance to T. spiralis infection in the muscle phase but not in the intestinal phase. Furthermore, fewer eosinophils around the nurse cells and reduced total and T. spiralis‐specific IgE in the serum were observed in CCR7‐blocked mice compared to those infected with only T. spiralis. CCR7 blockade led to the T. spiralis infection‐induced suppression of Th2‐ and Treg‐related cytokine production in vitro. These results suggest that CCR7 in DCs might play an essential role in host defence mechanisms against T. spiralis infection, particularly in the muscle stage of the infection, by accelerating Th2 and Treg cell responses.
{"title":"Trichinella spiralis nurse cell formation is regulated via CCR7+ dendritic cells","authors":"Mi-Kyung Park, S. Kang, M. Cho, H. Yu","doi":"10.1111/pim.12938","DOIUrl":"https://doi.org/10.1111/pim.12938","url":null,"abstract":"The chemokine receptor CCR7 is a well‐established homing receptor for dendritic cells (DCs) and T‐cells. Interaction with the CCL19 and CCL21 ligands promotes priming of immune responses in lymphoid tissues; however, the mechanism underlying CCR7‐induced immune responses against helminth parasite infection remains unknown. Thus, we examined the role of CCR7 in generating protective immune responses against intracellular Trichinella spiralis infection. The results showed significantly increased CCR7, CCL19 and CCL21 expression in the muscle tissue compared to that in the intestinal tissue in T. spiralis‐infected mice. The CCR7‐expressing DC population increased in the mesenteric and peripheral lymph nodes (PLNs) during T. spiralis infection. Notably, the number of CCR7‐expressing cells in PLNs increased by more than 30% at 28 days post‐infection; however, this increase was significantly inhibited in CCR7‐blocked mice treated with CCR7‐specific antibodies. T helper 2 (Th2)‐and regulatory T (Treg)‐related cytokine levels were also reduced by CCR7‐specific antibody treatment. CCR7‐blocked mice lost their resistance to T. spiralis infection in the muscle phase but not in the intestinal phase. Furthermore, fewer eosinophils around the nurse cells and reduced total and T. spiralis‐specific IgE in the serum were observed in CCR7‐blocked mice compared to those infected with only T. spiralis. CCR7 blockade led to the T. spiralis infection‐induced suppression of Th2‐ and Treg‐related cytokine production in vitro. These results suggest that CCR7 in DCs might play an essential role in host defence mechanisms against T. spiralis infection, particularly in the muscle stage of the infection, by accelerating Th2 and Treg cell responses.","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2022-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89551704","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}
Yan-mei Huang, Yu Chen, Yuxuan Liu, R. Mi, Xiangan Han, Haiyan Gong, Long Cheng, Zhaoguo Chen
Until now, no completely effective parasite‐specific drugs or vaccines have been approved for the treatment of cryptosporidiosis. Through the separation and identification of the sporozoite membrane protein of Cryptosporidium parvum (C. parvum), 20 related proteins were obtained. Among them, a calmodulin‐like protein (CML) has a similar functional domain‐exchange factor hand (EF‐hand) motif as calmodulin proteins (CaMs), so it may play a similarly important role in the invasion process. A 663 bp full gene encoding the C. parvum calmodulin‐like protein (CpCML) was inserted in pET28a vector and expressed in Escherichia coli. An immunofluorescence assay showed that CpCML was mainly located on the surface of the sporozoites. Three‐week‐old female BALB/c mice were used for modelling the immunoreactions and immunoprotection of recombinant CpCML (rCpCML) against artificial Cryptosporidium tyzzeri infections. The results indicated a significantly increased in anti‐CpCML antibody response, which was induced by the immunized recombinant protein. Compared to rP23 (recombinant P23), GST6P‐1 (expressed by pGEX‐6P‐1 transfected E. coli), GST4T‐1 (expressed by pGEX‐4T‐1 transfected E. coli), glutathione (GSH), adjuvant and blank control groups, rCpCML‐immunized mice produced specific spleen cell proliferation in addition to different production levels of IL‐2, IFN‐γ, TNF‐α, IL‐4 and IL‐5. Additionally, immunization with rCpCML led to 34.08% reduction of oocyst shedding in C. tyzzeri infected mice faeces which was similar to rP23. These results suggest that CpCML may be developed as a potential vaccine candidate antigen against cryptosporidiosis.
到目前为止,还没有完全有效的寄生虫特异性药物或疫苗被批准用于治疗隐孢子虫病。通过对细小隐孢子虫(Cryptosporidium parvum)孢子子膜蛋白的分离鉴定,得到20个相关蛋白。其中,钙调蛋白样蛋白(calmodulin - like protein, CML)具有与钙调蛋白(calmodulin proteins, CaMs)相似的功能域交换因子手(domain - exchange factor hand, EF - hand)基序,因此它可能在侵袭过程中发挥类似的重要作用。在pET28a载体中插入了一个663 bp的编码小弧菌钙调蛋白样蛋白(CpCML)的全基因,并在大肠杆菌中表达。免疫荧光分析显示CpCML主要位于孢子体表面。用3周龄雌性BALB/c小鼠模拟重组CpCML (rCpCML)对人工隐孢子虫感染的免疫反应和免疫保护作用。结果表明,免疫重组蛋白诱导的抗CpCML抗体应答显著增加。与rP23(重组P23)、GST6P‐1(由pGEX‐6P‐1转染的大肠杆菌表达)、GST4T‐1(由pGEX‐4T‐1转染的大肠杆菌表达)、谷胱甘肽(GSH)、佐剂和空白对照组相比,rCpCML‐免疫小鼠除了产生不同水平的IL‐2、IFN‐γ、TNF‐α、IL‐4和IL‐5外,还产生了特异性的脾细胞增殖。此外,rCpCML免疫后,tyzzeri感染小鼠粪便中卵囊脱落量减少34.08%,与rP23相似。这些结果提示CpCML可能作为潜在的隐孢子虫病疫苗候选抗原。
{"title":"Isolation and identification of sporozoite membrane protein of Cryptosporidium parvum and evaluation of calmodulin‐like protein immune protection","authors":"Yan-mei Huang, Yu Chen, Yuxuan Liu, R. Mi, Xiangan Han, Haiyan Gong, Long Cheng, Zhaoguo Chen","doi":"10.1111/pim.12937","DOIUrl":"https://doi.org/10.1111/pim.12937","url":null,"abstract":"Until now, no completely effective parasite‐specific drugs or vaccines have been approved for the treatment of cryptosporidiosis. Through the separation and identification of the sporozoite membrane protein of Cryptosporidium parvum (C. parvum), 20 related proteins were obtained. Among them, a calmodulin‐like protein (CML) has a similar functional domain‐exchange factor hand (EF‐hand) motif as calmodulin proteins (CaMs), so it may play a similarly important role in the invasion process. A 663 bp full gene encoding the C. parvum calmodulin‐like protein (CpCML) was inserted in pET28a vector and expressed in Escherichia coli. An immunofluorescence assay showed that CpCML was mainly located on the surface of the sporozoites. Three‐week‐old female BALB/c mice were used for modelling the immunoreactions and immunoprotection of recombinant CpCML (rCpCML) against artificial Cryptosporidium tyzzeri infections. The results indicated a significantly increased in anti‐CpCML antibody response, which was induced by the immunized recombinant protein. Compared to rP23 (recombinant P23), GST6P‐1 (expressed by pGEX‐6P‐1 transfected E. coli), GST4T‐1 (expressed by pGEX‐4T‐1 transfected E. coli), glutathione (GSH), adjuvant and blank control groups, rCpCML‐immunized mice produced specific spleen cell proliferation in addition to different production levels of IL‐2, IFN‐γ, TNF‐α, IL‐4 and IL‐5. Additionally, immunization with rCpCML led to 34.08% reduction of oocyst shedding in C. tyzzeri infected mice faeces which was similar to rP23. These results suggest that CpCML may be developed as a potential vaccine candidate antigen against cryptosporidiosis.","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2022-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90473631","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}