C-type lectin receptors (CLRs) constitute a category of innate immune receptors that play an essential role in the antifungal immune response. For over two decades, scientists have uncovered what are the fungal ligands recognized by CLRs and how these receptors initiate the immune response. Such studies have allowed the identification of genetic polymorphisms in genes encoding for CLRs or for proteins involved in the signalisation cascade they trigger. Nevertheless, our understanding of how these receptors functions and the full extent of their function during the antifungal immune response is still at its infancy. In this review, we summarize some of the main findings about CLRs in antifungal immunity and discuss what the future might hold for the field.
{"title":"C-type lectin receptors in antifungal immunity: Current knowledge and future developments.","authors":"Remi Hatinguais, Janet A Willment, Gordon D Brown","doi":"10.1111/pim.12951","DOIUrl":"https://doi.org/10.1111/pim.12951","url":null,"abstract":"<p><p>C-type lectin receptors (CLRs) constitute a category of innate immune receptors that play an essential role in the antifungal immune response. For over two decades, scientists have uncovered what are the fungal ligands recognized by CLRs and how these receptors initiate the immune response. Such studies have allowed the identification of genetic polymorphisms in genes encoding for CLRs or for proteins involved in the signalisation cascade they trigger. Nevertheless, our understanding of how these receptors functions and the full extent of their function during the antifungal immune response is still at its infancy. In this review, we summarize some of the main findings about CLRs in antifungal immunity and discuss what the future might hold for the field.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10078331/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9853468","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}
Human fungal pathogens cause a broad plethora of infections, spanning cutaneous dermatophytoses to invasive infections in immunocompromised hosts. As eukaryotic pathogens are capable of morphotype switching, they present unique challenges both for drug development and the immunological response. Whilst current antifungal therapies are limited to the orally available triazoles, intravenous echonocandins and polyenes, and flucytosine and terbinafine, there has been recent significant progress in the antifungal armamentorium with ibrexafungerp, a novel orally available terpanoid that inhibits 1,3-beta-D-glucan-approved by Food and Drug Administration in 2021, and fosmanogepix, an orally available pro-drug of manogepix, which targets glycosylphosphatidylinositol-anchored protein maturation entering Phase 3 studies for candidaemia. A number of further candidates are in development. There has been significant use of existing immunotherapies such as recombinant interferon-γ and G-CSF for fungal disease in immunocompromised patients, and there are emerging opportunities for monoclonal antibodies targeting TH2 inflammation. Omalizumab, an anti-IgE monoclonal antibody in asthma, is now used routinely for the treatment of allergic bronchopulmonary aspergillosis, and further agents targeting IL-4 and IL-5 are being evaluated. In addition, T-cell CAR therapy is showing early promise for fungal disease. Thus, we are likely to see rapid advances to our approach to the management of fungal disease in the near future.
{"title":"Antifungal chemotherapies and immunotherapies for the future.","authors":"Darius Armstrong-James","doi":"10.1111/pim.12960","DOIUrl":"https://doi.org/10.1111/pim.12960","url":null,"abstract":"<p><p>Human fungal pathogens cause a broad plethora of infections, spanning cutaneous dermatophytoses to invasive infections in immunocompromised hosts. As eukaryotic pathogens are capable of morphotype switching, they present unique challenges both for drug development and the immunological response. Whilst current antifungal therapies are limited to the orally available triazoles, intravenous echonocandins and polyenes, and flucytosine and terbinafine, there has been recent significant progress in the antifungal armamentorium with ibrexafungerp, a novel orally available terpanoid that inhibits 1,3-beta-D-glucan-approved by Food and Drug Administration in 2021, and fosmanogepix, an orally available pro-drug of manogepix, which targets glycosylphosphatidylinositol-anchored protein maturation entering Phase 3 studies for candidaemia. A number of further candidates are in development. There has been significant use of existing immunotherapies such as recombinant interferon-γ and G-CSF for fungal disease in immunocompromised patients, and there are emerging opportunities for monoclonal antibodies targeting TH2 inflammation. Omalizumab, an anti-IgE monoclonal antibody in asthma, is now used routinely for the treatment of allergic bronchopulmonary aspergillosis, and further agents targeting IL-4 and IL-5 are being evaluated. In addition, T-cell CAR therapy is showing early promise for fungal disease. Thus, we are likely to see rapid advances to our approach to the management of fungal disease in the near future.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10078527/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10417671","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}
Parasite ImmunologyVolume 45, Issue 2 e12972 FEATURED COVERFree Access Featured Cover First published: 27 January 2023 https://doi.org/10.1111/pim.12972AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Graphical Abstract Cover Illustration: The image is of Aspergillus spores on top of epithelium. Credit: The cover image has been provided by Darren Thomson, an expert at generating beautiful microscope images of fungi. He is based within the Medical Research Council Centre for Medical Mycology at the University of Exeter. Volume45, Issue2Special Issue: Fungal ImmunityFebruary 2023e12972 RelatedInformation
{"title":"Featured Cover","authors":"","doi":"10.1111/pim.12972","DOIUrl":"https://doi.org/10.1111/pim.12972","url":null,"abstract":"Parasite ImmunologyVolume 45, Issue 2 e12972 FEATURED COVERFree Access Featured Cover First published: 27 January 2023 https://doi.org/10.1111/pim.12972AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Graphical Abstract Cover Illustration: The image is of Aspergillus spores on top of epithelium. Credit: The cover image has been provided by Darren Thomson, an expert at generating beautiful microscope images of fungi. He is based within the Medical Research Council Centre for Medical Mycology at the University of Exeter. Volume45, Issue2Special Issue: Fungal ImmunityFebruary 2023e12972 RelatedInformation","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135794605","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}
Retraction: Ajay Kumar, Sushmita Das, Abhishek Mandal, Sudha Verma, Kumar Abhishek, Ashish Kumar, Vinod Kumar, Ayan Kumar Ghosh, Pradeep Das (2018) Leishmania infection activates host mTOR for its survival by M2 macrophage polarization. Parasite Immunology 40(11): e12586; https://doi.org/10.1111/pim.12586 The above article, published online on 6 September 2018, in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editors-in-Chief, Eleanor M. Riley and Richard K. Grencis, and John Wiley and Sons Ltd. Following publication, concerns were raised by third parties regarding Figures 4b, 5b and 8b. The authors were unable to provide a satisfactory explanation and could not provide the original data. The retraction has been agreed because of concerns that the figures were duplicated, affecting the interpretation of the data and results presented.
撤回:Ajay Kumar, Sushmita Das, Abhishek Mandal, Sudha Verma, Kumar Abhishek, Ashish Kumar, Vinod Kumar, Ayan Kumar Ghosh, Pradeep Das(2018)利什曼原虫感染通过M2巨噬细胞极化激活宿主mTOR存活。寄生虫免疫学40(11):e12586;https://doi.org/10.1111/pim.12586上述文章于2018年9月6日在线发表在Wiley在线图书馆(wileyonlinelibrary.com)上,经期刊主编Eleanor M. Riley和Richard K. Grencis以及John Wiley and Sons Ltd.同意撤回。在公布后,第三方对图4b、5b及8b表示关注。作者无法提供令人满意的解释,也无法提供原始数据。由于担心数据重复,影响对所提供数据和结果的解释,已同意撤回。
{"title":"Retraction.","authors":"","doi":"10.1111/pim.12958","DOIUrl":"https://doi.org/10.1111/pim.12958","url":null,"abstract":"<p><p>Retraction: Ajay Kumar, Sushmita Das, Abhishek Mandal, Sudha Verma, Kumar Abhishek, Ashish Kumar, Vinod Kumar, Ayan Kumar Ghosh, Pradeep Das (2018) Leishmania infection activates host mTOR for its survival by M2 macrophage polarization. Parasite Immunology 40(11): e12586; https://doi.org/10.1111/pim.12586 The above article, published online on 6 September 2018, in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editors-in-Chief, Eleanor M. Riley and Richard K. Grencis, and John Wiley and Sons Ltd. Following publication, concerns were raised by third parties regarding Figures 4b, 5b and 8b. The authors were unable to provide a satisfactory explanation and could not provide the original data. The retraction has been agreed because of concerns that the figures were duplicated, affecting the interpretation of the data and results presented.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10767588","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}
Shiming Jiao, Nie Tan, Chengyu Zhu, Yong Fu, Kun Zhang, Yan Ding, Wenyue Xu
Viral infection often induce the expression of murine fibrinogen-like protein 2 (mFGL2) triggering immune coagulation, which causes severe liver pathogenesis via increased fibrin deposition and thrombosis in the microvasculature. We aimed to investigate the role of mFGL2 in the liver stage of malaria infections. We reveal that infection with malaria sporozoites also induces increased expression of mFGL2 and that this expression is primarily located within the liver Kupffer and endothelial cells. In addition, we report that inhibition of FGL2 has no significant effect on immune coagulation but increases the expression of inflammatory cytokines in the livers of infected mice. Interestingly, FGL2 deficiency had no significant impact on the development of liver stage malaria parasites or the pathogenesis of the infected liver. In contrast to viral infections, we conclude that mFGL2 does not contribute to either parasite development or liver pathology during these infections, revealing the unique features of this protein in liver-stage malaria infections.
{"title":"The distinctive role of membrane fibrinogen-like protein 2 in the liver stage of rodent malaria infections.","authors":"Shiming Jiao, Nie Tan, Chengyu Zhu, Yong Fu, Kun Zhang, Yan Ding, Wenyue Xu","doi":"10.1111/pim.12956","DOIUrl":"https://doi.org/10.1111/pim.12956","url":null,"abstract":"<p><p>Viral infection often induce the expression of murine fibrinogen-like protein 2 (mFGL2) triggering immune coagulation, which causes severe liver pathogenesis via increased fibrin deposition and thrombosis in the microvasculature. We aimed to investigate the role of mFGL2 in the liver stage of malaria infections. We reveal that infection with malaria sporozoites also induces increased expression of mFGL2 and that this expression is primarily located within the liver Kupffer and endothelial cells. In addition, we report that inhibition of FGL2 has no significant effect on immune coagulation but increases the expression of inflammatory cytokines in the livers of infected mice. Interestingly, FGL2 deficiency had no significant impact on the development of liver stage malaria parasites or the pathogenesis of the infected liver. In contrast to viral infections, we conclude that mFGL2 does not contribute to either parasite development or liver pathology during these infections, revealing the unique features of this protein in liver-stage malaria infections.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10492279","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}
Retraction: RajKishor Pandey, Manas Ranjan Dikhit, Avinash Kumar, Budheswar Dehury, Krishna Pandey, Roshan Kamal Topno, Pradeep Das, Sanjiva Bimal (2020) Evaluating the immunomodulatory responses of LdODC-derived MHC Class-II restricted peptides against VL. Parasite Immunology 42(4): e12699; https://doi.org/10.1111/pim.12699 The above article, published online on 24 January 2020, in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editors-in-Chief, Eleanor M. Riley and Richard K. Grencis, and John Wiley and Sons Ltd. Following publication, concerns were raised by a third party regarding similarities in Figures 3 and 5. The authors were unable to provide a satisfactory explanation and could not provide the original data. The retraction has been agreed because of concerns that the figures were duplicated, affecting the interpretation of the data and results presented.
撤回:RajKishor Pandey, Manas Ranjan Dikhit, Avinash Kumar, Budheswar Dehury, Krishna Pandey, Roshan Kamal Topno, Pradeep Das, Sanjiva Bimal(2020)评估ldodc衍生的MHC ii类限制性肽对VL的免疫调节反应。寄生虫免疫学42(4):e12699;https://doi.org/10.1111/pim.12699上述文章于2020年1月24日在线发表在Wiley在线图书馆(wileyonlinelibrary.com)上,经期刊主编Eleanor M. Riley和Richard K. Grencis以及John Wiley and Sons Ltd.同意撤回。在发布之后,第三方对图3和图5中的相似性提出了担忧。作者无法提供令人满意的解释,也无法提供原始数据。由于担心数据重复,影响对所提供数据和结果的解释,已同意撤回。
{"title":"Retraction.","authors":"","doi":"10.1111/pim.12959","DOIUrl":"https://doi.org/10.1111/pim.12959","url":null,"abstract":"<p><p>Retraction: RajKishor Pandey, Manas Ranjan Dikhit, Avinash Kumar, Budheswar Dehury, Krishna Pandey, Roshan Kamal Topno, Pradeep Das, Sanjiva Bimal (2020) Evaluating the immunomodulatory responses of LdODC-derived MHC Class-II restricted peptides against VL. Parasite Immunology 42(4): e12699; https://doi.org/10.1111/pim.12699 The above article, published online on 24 January 2020, in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editors-in-Chief, Eleanor M. Riley and Richard K. Grencis, and John Wiley and Sons Ltd. Following publication, concerns were raised by a third party regarding similarities in Figures 3 and 5. The authors were unable to provide a satisfactory explanation and could not provide the original data. The retraction has been agreed because of concerns that the figures were duplicated, affecting the interpretation of the data and results presented.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10416866","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 : 2022-12-01Epub Date: 2022-10-04DOI: 10.1111/pim.12952
Margaret R Smith, Komi Gbedande, Corey M Johnson, Logan A Campbell, Robert S Onjiko, Nadia D Domingo, Michael M Opata
Severe malaria occurs most in young children but is poorly understood due to the absence of a developmentally-equivalent rodent model to study the pathogenesis of the disease. Though functional and quantitative deficiencies in innate response and a biased T helper 1 (Th1) response are reported in newborn pups, there is little information available about this intermediate stage of the adaptive immune system in murine neonates. To fill this gap in knowledge, we have developed a mouse model of severe malaria in young mice using 15-day old mice (pups) infected with Plasmodium chabaudi. We observe similar parasite growth pattern in pups and adults, with a 60% mortality and a decrease in the growth rate of the surviving young mice. Using a battery of behavioral assays, we observed neurological symptoms in pups that do not occur in infected wildtype adults. CD4+ T cells were activated and differentiated to an effector T cell (Teff) phenotype in both adult and pups. However, there were relatively fewer and less terminally differentiated pup CD4+ Teff than adult Teff. Interestingly, despite less activation, the pup Teff expressed higher T-bet than adults' cells. These data suggest that Th1 cells are functional in pups during Plasmodium infection but develop slowly.
重症疟疾多发于幼儿,但由于缺乏与发育相当的啮齿类动物模型来研究该病的发病机制,人们对其了解甚少。虽然有报道称新生幼鼠先天性反应的功能和数量缺陷以及有偏向的 T 辅助细胞 1(Th1)反应,但有关鼠类新生儿适应性免疫系统这一中间阶段的信息却很少。为了填补这一知识空白,我们利用感染了沙鲍迪疟原虫的 15 天龄小鼠(幼鼠),建立了幼鼠重症疟疾模型。我们观察到幼鼠和成鼠体内寄生虫的生长模式相似,存活的幼鼠死亡率为 60%,生长速度下降。通过一系列行为测定,我们观察到幼鼠出现神经症状,而野生型成鼠感染后不会出现这些症状。成年小鼠和幼鼠的 CD4+ T 细胞都被激活并分化成效应 T 细胞(Teff)表型。然而,与成体Teff相比,幼体CD4+Teff的数量相对较少,终末分化的程度也较低。有趣的是,尽管活化程度较低,幼犬Teff表达的T-bet却高于成犬细胞。这些数据表明,在疟原虫感染期间,幼崽体内的 Th1 细胞具有功能性,但发育缓慢。
{"title":"Model of severe malaria in young mice suggests unique response of CD4 T cells.","authors":"Margaret R Smith, Komi Gbedande, Corey M Johnson, Logan A Campbell, Robert S Onjiko, Nadia D Domingo, Michael M Opata","doi":"10.1111/pim.12952","DOIUrl":"10.1111/pim.12952","url":null,"abstract":"<p><p>Severe malaria occurs most in young children but is poorly understood due to the absence of a developmentally-equivalent rodent model to study the pathogenesis of the disease. Though functional and quantitative deficiencies in innate response and a biased T helper 1 (Th1) response are reported in newborn pups, there is little information available about this intermediate stage of the adaptive immune system in murine neonates. To fill this gap in knowledge, we have developed a mouse model of severe malaria in young mice using 15-day old mice (pups) infected with Plasmodium chabaudi. We observe similar parasite growth pattern in pups and adults, with a 60% mortality and a decrease in the growth rate of the surviving young mice. Using a battery of behavioral assays, we observed neurological symptoms in pups that do not occur in infected wildtype adults. CD4<sup>+</sup> T cells were activated and differentiated to an effector T cell (Teff) phenotype in both adult and pups. However, there were relatively fewer and less terminally differentiated pup CD4<sup>+</sup> Teff than adult Teff. Interestingly, despite less activation, the pup Teff expressed higher T-bet than adults' cells. These data suggest that Th1 cells are functional in pups during Plasmodium infection but develop slowly.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":null,"pages":null},"PeriodicalIF":1.4,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9787679/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10445795","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 : 2022-12-01Epub Date: 2022-10-14DOI: 10.1111/pim.12954
Natália Berne Pinheiro, Emanuelle Baldo Gaspar, Alessandro Pelegrine Minho, Robert Domingues, Micaele Quintana de Moura, Antônio Sergio Varela Junior, Gabriela de Almeida Capella, Adriane Leites Strothmann, Wesley Douglas Terto, Fabio Pereira Leivas Leite
Haemonchus contortus is the most pathogenic parasite for sheep. The objective was to evaluate immunomodulation of the probiotic Saccharomyces boulardii in sheep experimentally infected with H. contortus. Twenty-four sheep were divided into three groups: one infected with 500 H. contortus larvae/day for 26 days and supplemented with S. boulardii (40 ml with 1 × 108 CFU/ml/day); a control group only infected with H. contortus but not supplemented; and a naïve group that never came into contact with either parasites or S. boulardii. To assess the humoral immune response, production of specific serum IgG anti-somatic H. contortus antigen was evaluated through indirect ELISA. To assess the cellular immune response, cell populations and cytokine (IL-4, IL-5 and IL-10) production were evaluated through flow cytometry. For parasitological analyses, the counts of eggs per gram of faeces (EPG) and larvae per faecal culture were assessed. At all the study points, the concentration of IgG anti-H. contortus was higher (p < .05) in the S. boulardii group than in the other groups. The cell analysis revealed that there were significantly higher numbers (p < .05) of cells expressing MHC-II and significantly higher numbers (p < .05) of eosinophils in the mucosa in the S. boulardii group. Significant expression of IL-10 was observed only in the control infected group. There were significant reductions (p < .05) in EPG and larval counts in the S. boulardii supplemented group. These results show that S. boulardii supplementation modulated the immune response against H. contortus, thereby reducing its infection.
{"title":"Sheep immune-stimulated with Saccharomyces boulardii show reduced prolificacy of Haemonchus contortus.","authors":"Natália Berne Pinheiro, Emanuelle Baldo Gaspar, Alessandro Pelegrine Minho, Robert Domingues, Micaele Quintana de Moura, Antônio Sergio Varela Junior, Gabriela de Almeida Capella, Adriane Leites Strothmann, Wesley Douglas Terto, Fabio Pereira Leivas Leite","doi":"10.1111/pim.12954","DOIUrl":"https://doi.org/10.1111/pim.12954","url":null,"abstract":"<p><p>Haemonchus contortus is the most pathogenic parasite for sheep. The objective was to evaluate immunomodulation of the probiotic Saccharomyces boulardii in sheep experimentally infected with H. contortus. Twenty-four sheep were divided into three groups: one infected with 500 H. contortus larvae/day for 26 days and supplemented with S. boulardii (40 ml with 1 × 10<sup>8</sup> CFU/ml/day); a control group only infected with H. contortus but not supplemented; and a naïve group that never came into contact with either parasites or S. boulardii. To assess the humoral immune response, production of specific serum IgG anti-somatic H. contortus antigen was evaluated through indirect ELISA. To assess the cellular immune response, cell populations and cytokine (IL-4, IL-5 and IL-10) production were evaluated through flow cytometry. For parasitological analyses, the counts of eggs per gram of faeces (EPG) and larvae per faecal culture were assessed. At all the study points, the concentration of IgG anti-H. contortus was higher (p < .05) in the S. boulardii group than in the other groups. The cell analysis revealed that there were significantly higher numbers (p < .05) of cells expressing MHC-II and significantly higher numbers (p < .05) of eosinophils in the mucosa in the S. boulardii group. Significant expression of IL-10 was observed only in the control infected group. There were significant reductions (p < .05) in EPG and larval counts in the S. boulardii supplemented group. These results show that S. boulardii supplementation modulated the immune response against H. contortus, thereby reducing its infection.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33487855","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 : 2022-12-01Epub Date: 2022-10-17DOI: 10.1111/pim.12950
Wenxuan Wang, Tanghui Xie, Fan Jiang, Yaoxin Jiang, Zhe Jin, Zhe Yang, Mei Kong, Lei Cheng, Liangliang Fu, Xiaoyong Du
Haemonchus contortus (H. contortus) has caused a huge impact on the animal husbandry economy in the world's tropical and subtropical regions. Innate immunity is the first-line of host defence. The host recognizes pathogen-associated molecular patterns (PAMPs) through a variety of pattern recognition receptors (PRRs) and activates downstream signalling pathways to resist pathogens invasion. Therefore, elucidating the immune interaction between host and pathogen is key to understanding how the host resists the pathogen. We identified 1516 protein-protein interactions (PPIs) between goat innate immune signal pathway proteins and H. contortus excretory-secretory proteins (ESPs) by Recombination-based "Library vs. Library" yeast two-hybrid system (RLL-Y2H) and constructed the PPIs network. Among them, the NLR and IL-17 signalling pathways have the most protein interactions. And there were more interaction proteins between NOD1 and MUC5AC proteins in the pathways. Combined with the differentially expressed genes (DEGs) of susceptible and resistant goats identified in the preliminary work of our laboratory, we selected the intersection genes to construct the PPIs network, and TRAF2 appeared as a key protein of goat innate immune signalling pathway. We initially studied the PPIs between goat and H. contortus ESPs, which provides valuable information for better understanding the immune interaction between the goats and the H. contortus.
弯血蜱(Haemonchus contortus)对世界热带和亚热带地区的畜牧业经济造成了巨大的影响。先天免疫是宿主防御的第一道防线。宿主通过多种模式识别受体(PRRs)识别病原体相关分子模式(PAMPs),并激活下游信号通路来抵抗病原体的入侵。因此,阐明宿主与病原体之间的免疫相互作用是了解宿主如何抵抗病原体的关键。利用基于重组的“Library vs. Library”酵母双杂交系统(RLL-Y2H)鉴定山羊先天免疫信号通路蛋白与弯弯鼠分泌蛋白(ESPs)之间的1516个蛋白-蛋白相互作用(PPIs),并构建了PPIs网络。其中NLR和IL-17信号通路蛋白相互作用最多。NOD1与MUC5AC蛋白之间存在较多的相互作用蛋白。结合本实验室前期工作中鉴定的易感山羊和耐药山羊的差异表达基因(DEGs),选择交叉基因构建PPIs网络,TRAF2作为山羊先天免疫信号通路的关键蛋白出现。本研究初步研究了山羊与弯形血鼠ESPs之间的PPIs,为更好地了解山羊与弯形血鼠之间的免疫相互作用提供了有价值的信息。
{"title":"Protein interactions network of goat innate immune signalling pathway proteins and Haemonchus contortus excretory-secretory proteins.","authors":"Wenxuan Wang, Tanghui Xie, Fan Jiang, Yaoxin Jiang, Zhe Jin, Zhe Yang, Mei Kong, Lei Cheng, Liangliang Fu, Xiaoyong Du","doi":"10.1111/pim.12950","DOIUrl":"https://doi.org/10.1111/pim.12950","url":null,"abstract":"<p><p>Haemonchus contortus (H. contortus) has caused a huge impact on the animal husbandry economy in the world's tropical and subtropical regions. Innate immunity is the first-line of host defence. The host recognizes pathogen-associated molecular patterns (PAMPs) through a variety of pattern recognition receptors (PRRs) and activates downstream signalling pathways to resist pathogens invasion. Therefore, elucidating the immune interaction between host and pathogen is key to understanding how the host resists the pathogen. We identified 1516 protein-protein interactions (PPIs) between goat innate immune signal pathway proteins and H. contortus excretory-secretory proteins (ESPs) by Recombination-based \"Library vs. Library\" yeast two-hybrid system (RLL-Y2H) and constructed the PPIs network. Among them, the NLR and IL-17 signalling pathways have the most protein interactions. And there were more interaction proteins between NOD1 and MUC5AC proteins in the pathways. Combined with the differentially expressed genes (DEGs) of susceptible and resistant goats identified in the preliminary work of our laboratory, we selected the intersection genes to construct the PPIs network, and TRAF2 appeared as a key protein of goat innate immune signalling pathway. We initially studied the PPIs between goat and H. contortus ESPs, which provides valuable information for better understanding the immune interaction between the goats and the H. contortus.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":null,"pages":null},"PeriodicalIF":2.2,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40355420","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 : 2022-11-01Epub Date: 2022-09-23DOI: 10.1111/pim.12947
Rafaelle de Paula Freire, Francisco Rafael Marciano Fonseca, Naya Lúcia Rodrigues de Castro, Carrel Xavier Martins Lima, Raquel Peralva Ribeiro-Romão, Diane Isabelle Magno Cavalcante, Clarissa Romero Teixeira, Regis Gomes, Alda Maria Da-Cruz, Maria Jania Teixeira
The golden hamster (Mesocricetus auratus) is commonly used as a promising model for Leishmania braziliensis infection developing skin-ulcerated lesions. However, different protocols using high concentration of parasites inoculated in the footpad result in severe clinical disease. Here, we further investigate the outcome of the site of infection and concentration of L. braziliensis parasites inoculated on the immunopathogenesis and clinical evolution. Initially, hamsters were infected in the ear dermis or hind footpad with a concentration of 1 × 105 parasites. Animals infected in the ear dermis developed a disease, with an increased parasite load that more closely resembled human cutaneous leishmaniasis lesions comparing to the group infected in the footpad. Next, we evaluated if different parasite concentrations (104 , 105 and 106 ) inoculated in the ear dermis would impact the course and clinical aspects of infection. Hamsters infected with 104 and 105 parasites developed mild lesions compared to the group infected with 106 that presented severe and persistent lesions. The parasite load varied between the different parasite concentrations. The inflammatory response was more intense when infection was initiated with 106 parasites accompanied by an increased initial expression of IL-4, IL-10 and arginase in the lymph node followed by expression of both pro-and anti-inflammatory cytokines comparing to groups infected with 104 and 105 parasites. In conclusion, the number of parasites inoculated, and the initial site of infection could influence the inflammatory response, and clinical presentation. Our results suggest that the ear dermis infection model induces a chronic disease that relates to immunopathological aspects of CL natural infection.
{"title":"Different inoculum of Leishmania braziliensis concentrations influence immunopathogenesis and clinical evolution in the ear dermis hamster model of cutaneous leishmaniasis.","authors":"Rafaelle de Paula Freire, Francisco Rafael Marciano Fonseca, Naya Lúcia Rodrigues de Castro, Carrel Xavier Martins Lima, Raquel Peralva Ribeiro-Romão, Diane Isabelle Magno Cavalcante, Clarissa Romero Teixeira, Regis Gomes, Alda Maria Da-Cruz, Maria Jania Teixeira","doi":"10.1111/pim.12947","DOIUrl":"https://doi.org/10.1111/pim.12947","url":null,"abstract":"<p><p>The golden hamster (Mesocricetus auratus) is commonly used as a promising model for Leishmania braziliensis infection developing skin-ulcerated lesions. However, different protocols using high concentration of parasites inoculated in the footpad result in severe clinical disease. Here, we further investigate the outcome of the site of infection and concentration of L. braziliensis parasites inoculated on the immunopathogenesis and clinical evolution. Initially, hamsters were infected in the ear dermis or hind footpad with a concentration of 1 × 10<sup>5</sup> parasites. Animals infected in the ear dermis developed a disease, with an increased parasite load that more closely resembled human cutaneous leishmaniasis lesions comparing to the group infected in the footpad. Next, we evaluated if different parasite concentrations (10<sup>4</sup> , 10<sup>5</sup> and 10<sup>6</sup> ) inoculated in the ear dermis would impact the course and clinical aspects of infection. Hamsters infected with 10<sup>4</sup> and 10<sup>5</sup> parasites developed mild lesions compared to the group infected with 10<sup>6</sup> that presented severe and persistent lesions. The parasite load varied between the different parasite concentrations. The inflammatory response was more intense when infection was initiated with 10<sup>6</sup> parasites accompanied by an increased initial expression of IL-4, IL-10 and arginase in the lymph node followed by expression of both pro-and anti-inflammatory cytokines comparing to groups infected with 10<sup>4</sup> and 10<sup>5</sup> parasites. In conclusion, the number of parasites inoculated, and the initial site of infection could influence the inflammatory response, and clinical presentation. Our results suggest that the ear dermis infection model induces a chronic disease that relates to immunopathological aspects of CL natural infection.</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":"40347488","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}