Parasite Immunology最新文献

{"title":"Organ-specific immune profiling of Leishmania donovani-infected hamsters.","authors":"Sheetal Saini,&nbsp;Bharat Singh,&nbsp;Anuradha Dube,&nbsp;Amogh Anant Sahasrabuddhe,&nbsp;Ambak Kumar Rai","doi":"10.1111/pim.12964","DOIUrl":"https://doi.org/10.1111/pim.12964","url":null,"abstract":"<p><p>Visceral leishmaniasis (VL) is a neglected disease with a broad spectrum of clinical manifestations and involvement of visceral organs. Organ-specific immune response against the Leishmania donovani (Ld) complex is not yet understood due to the unavailability of an appropriate experimental model. In reference to our recent work on comparing the hamster model with VL patients, it is now possible to understand immune profiling in different visceral organs. This may offer an answer to varying parasite loads in different visceral organs in the same host. Herein, we analysed a panel of immune markers (Th-2/Th-1) in visceral organs of Ld-infected hamsters and quantified parasitic load in the same tissues using qPCR assay. In spleen, liver, bone marrow and lymph node (mesenteric) from Ld-infected hamsters, the parasite burden was quantified along with mRNA expression of a panel of Th-2 and Th-1 type immune markers, namely IL-10, IL-4, Arginase-I, GATA-3, SOCS-3, IL-12, IFN-γ, iNOS, T-bet and SOCS-5. A clear dichotomy was absent between Th-2 and Th-1 type immune markers and the major players of this immune response were IFN-γ, IL-10, T-bet, GATA-3, SOCS-5 and SOCS-3.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"45 3","pages":"e12964"},"PeriodicalIF":2.2,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10761795","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}

{"title":"Host responses against the fish parasitizing ciliate Cryptocaryon irritans.","authors":"Shuiqing Jiang,&nbsp;Xiaohong Huang","doi":"10.1111/pim.12967","DOIUrl":"https://doi.org/10.1111/pim.12967","url":null,"abstract":"<p><p>The parasitic ciliate Cryptocaryon irritans, which infects almost all marine fish species occurring in both tropical and subtropical regions throughout the world. The disease, cryptocaryonosis, accounts for significant economic losses to the aquaculture industry. This review attempts to provide a comprehensive overview of the biology of the parasite, host-parasite interactions and both specific and non-specific host defense mechanisms are responsible for the protection of fish against challenge infections with this ciliate. Also, this article reflects the current interest in this subject area and the quest to develop an available vaccine against the disease. Due to the high frequency of clinical fish cryptocaryonosis, the study of fish immune responses to C. irritans provides an optimal experimental model for understanding immunity against extracellular protozoa.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"45 3","pages":"e12967"},"PeriodicalIF":2.2,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10768974","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}

{"title":"Role of antigen-presenting cells in non-ulcerated skin lesions caused by Leishmania (Leishmania) infantum chagasi.","authors":"Carmen M Sandoval Pacheco,&nbsp;Gabriela V Araujo Flores,&nbsp;Aurea F Ferreira,&nbsp;Vânia L R Matta,&nbsp;Claudia M Castro Gomes,&nbsp;Wilfredo H Sosa-Ochoa,&nbsp;Concepción Zúniga,&nbsp;Fernando T Silveira,&nbsp;Carlos E P Corbett,&nbsp;Márcia D Laurenti","doi":"10.1111/pim.12971","DOIUrl":"https://doi.org/10.1111/pim.12971","url":null,"abstract":"<p><p>In Central America, infection by Leishmania (Leishmania) infantum chagasi causes visceral leishmaniasis and non-ulcerated cutaneous leishmaniasis (NUCL). This work aimed to evaluate the participation of subpopulations of antigen-presenting cells in skin lesions of patients affected by NUCL through double-staining immunohistochemistry using cellular and intracellular markers. Twenty-three skin biopsies from patients affected by NUCL were used. Histological sections stained by HE were used for histopathological study. Immunohistochemical studies were performed using primary antibodies against Langerhans cells, dermal dendritic cells, T lymphocytes, and the cytokines IL-12, IFN-γ, TNF-α, iNOS, and IL-10. The histopathological lesions were characterized by an inflammatory infiltrate, predominantly lymphohistiocytic, of variable intensity, with a diffuse arrangement associated with epithelioid granulomas and discreet parasitism. Double-staining immunohistochemistry showed higher participation of dendritic cells producing the proinflammatory cytokine IL-12 in relation to the other evaluated cytokines. Activation of the cellular immune response was marked by a higher density of CD8 Tc1-lymphocytes followed by CD4 Th1-lymphocytes producing mainly IFN-γ. The data obtained in the present study suggest that antigen-presenting cells play an important role in the in situ immune response through the production of proinflammatory cytokines, directing the cellular immune response preferentially to the Th1 and Tc1 types in NUCL caused by L. (L.) infantum chagasi.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"45 3","pages":"e12971"},"PeriodicalIF":2.2,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10778302","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}

{"title":"Chemokine receptors on human regulatory T cells during cutaneous leishmaniasis.","authors":"Maria Carolina Accioly Brelaz de Castro,&nbsp;Rafael de Freitas E Silva,&nbsp;Marton Kaique de Andrade Cavalcante,&nbsp;Larissa Layne Soares Bezerra Silva,&nbsp;Fabiana Oliveira Dos Santos Gomes,&nbsp;Maria Edileuza Felinto de Brito,&nbsp;Valéria Rêgo Alves Pereira","doi":"10.1111/pim.12966","DOIUrl":"https://doi.org/10.1111/pim.12966","url":null,"abstract":"<p><p>The aim of this work was to define the population of regulatory T cells (Tregs) which are circulating in the blood of Leishmania infected individuals clinically displaying a lesion (active disease-AD) and sub-clinical (SC) ones. We have individually collected blood samples, processed the PBMC and stained with fluorochrome-conjugated antibodies against CD3, CD4, Foxp3, CD25, CTLA-4, Ki-67, CCR4, CCR5, and CCR7. Cells were analyzed by flow cytometry. Our results suggest that CD25 and CTLA-4 are upregulated in Tregs of AD patients when compared to SC and uninfected (UN) controls. Moreover, Tregs proliferate upon infection based on Ki-67 nuclear antigen staining. Finally, we have observed that these Tregs of SC and AD patients upregulate CCR4, but not CCR5 and CCR7. There is an increase in the number of circulating Tregs in the blood of Leishmania infected individuals. These cells are potentially more suppressive based on the increased upregulation of CD25 and CTLA-4 during clinical infection (AD) when compared to SC infection. Tregs of both SC and AD cohorts are proliferating and express CCR4, which potentially guide them to the skin, but do not upregulate CCR5 and CCR7.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"45 3","pages":"e12966"},"PeriodicalIF":2.2,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10768971","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}

{"title":"Emerging and re-emerging fungal threats in Africa.","authors":"Rachael Dangarembizi, Sean Wasserman, Jennifer Claire Hoving","doi":"10.1111/pim.12953","DOIUrl":"10.1111/pim.12953","url":null,"abstract":"<p><p>The emergence of deadly fungal infections in Africa is primarily driven by a disproportionately high burden of human immunodeficiency virus (HIV) infections, lack of access to quality health care, and the unavailability of effective antifungal drugs. Immunocompromised people in Africa are therefore at high risk of infection from opportunistic fungal pathogens such as Cryptococcus neoformans and Pneumocystis jirovecii, which are associated with high morbidity, mortality, and related socioeconomic impacts. Other emerging fungal threats include Emergomyces spp., Histoplasma spp., Blastomyces spp., and healthcare-associated multi-drug resistant Candida auris. Socioeconomic development and the Covid-19 pandemic may influence shifts in epidemiology of invasive fungal diseases on the continent. This review discusses the epidemiology, clinical manifestations, and current management strategies available for these emerging fungal diseases in Africa. We also discuss gaps in knowledge, policy, and research to inform future efforts at managing these fungal threats.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"45 2","pages":"e12953"},"PeriodicalIF":1.4,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9892204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9620876","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}

{"title":"New insights into immunity to skin fungi shape our understanding of health and disease.","authors":"Fiorella Ruchti,&nbsp;Salomé LeibundGut-Landmann","doi":"10.1111/pim.12948","DOIUrl":"https://doi.org/10.1111/pim.12948","url":null,"abstract":"<p><p>Fungi represent an integral part of the skin microbiota. Their complex interaction network with the host shapes protective immunity during homeostasis. If host defences are breached, skin-resident fungi including Malassezia and Candida, and environmental fungi such as dermatophytes can cause cutaneous infections. In addition, fungi are associated with diverse non-infectious skin disorders. Despite their multiple roles in health and disease, fungi remain elusive and understudied, and the mechanisms underlying the emergence of pathological conditions linked to fungi are largely unclear. The identification of IL-17 as an important antifungal effector mechanism represents a milestone for understanding homeostatic antifungal immunity. At the same time, host-adverse, disease-promoting roles of IL-17 have been delineated, as in psoriasis. Fungal dysbiosis represents another feature of many pathological skin conditions with an unknown causal link of intra- and interkingdom interactions to disease pathogenesis. The emergence of new fungal pathogens such as Candida auris highlights the need for more research into fungal immunology to understand how antifungal responses shape health and diseases. Recent technological advances for genetically manipulating fungi to target immunomodulatory fungal determinants, multi-omics approaches for studying immune cells in the human skin, and novel experimental models open up a promising future for skin fungal immunity.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"45 2","pages":"e12948"},"PeriodicalIF":2.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/b3/7a/PIM-45-0.PMC10078452.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9620858","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}

{"title":"Fungal pathogens: The underappreciated parasites that are now in the spotlight.","authors":"Peter C Cook,&nbsp;Rebecca A Drummond","doi":"10.1111/pim.12968","DOIUrl":"https://doi.org/10.1111/pim.12968","url":null,"abstract":"Fungi pose a significant threat to human health by causing a complex array of different diseases. These include superficial but potentially disfiguring infections, chronic allergic disorders and systemic lifethreatening fungal diseases, all of which have been estimated to affect over a billion people worldwide. Despite the significant threats that fungi pose, they are frequently overlooked and fungal-mediated deaths are under reported. There is an urgent need to improve our ability to diagnose fungal infections and develop improved therapeutics to combat these challenges. However, a significant challenge which has greatly impeded this progress is the mechanistic understanding of the fungal–host interactions which underpin disease. For this special issue in Parasite Immunology, a series of reviews explore the latest development within the field of fungal immunology by focusing on the role of the fungi as a pathogen versus commensal, the host immune response, emerging fungi species of concern and how these infections are treated. Each review also identifies key challenges and future opportunities which may achieve the goal of reducing the threat that fungi pose to human health. To understand anti-fungal defence, it is vital to reflect that we are constantly under threat from fungal infection and whether fungi are cleared, become commensals, or invade the tissue is the outcome of dynamic host–fungus interaction. Brown considers this and highlights how pathogenicity traits that promote infection have emerged independently across distinct phylogenetic branches of fungi allowing them to occupy different niches within the host. This review proposes the “Resilience Network” concept as a framework in which to understand how fungal pathogens can exhibit extraordinary diversity in their physiological robustness which underpins their immune evasion and drug resistance capability. Exciting future research goals are proposed to unravel this network with the tantalizing prospect that this will dramatically improve our therapeutic capability to combat fungal disease. Over the last 20 years, it has become apparent that commensals are a vital component in mediating human health and disease. Yet, the vast majority of research into this has focused on bacterial species despite the fact that the fungi are a major constituent of our commensal community (termed the “mycobiome”). Ruchti and LeibundGut– Landmann focus on evaluating what is known about the role of fungi as an integral part of the skin microbiota. They discuss how these fungi have the potential to trigger and exacerbate skin diseases, and the importance of host IL-17 cytokine mediated responses in the skin at combatting these infections. They also consider the impact of a newly emerged drug-resistant fungal species that colonizes the skin (Candida auris). However, much remains unknown about fungi–host interaction in the skin and the authors suggest how recent technological advances have the potential to ex","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"45 2","pages":"e12968"},"PeriodicalIF":2.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10291614","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}

{"title":"Fungal resilience and host-pathogen interactions: Future perspectives and opportunities.","authors":"Alistair J P Brown","doi":"10.1111/pim.12946","DOIUrl":"https://doi.org/10.1111/pim.12946","url":null,"abstract":"<p><p>We are constantly exposed to the threat of fungal infection. The outcome-clearance, commensalism or infection-depends largely on the ability of our innate immune defences to clear infecting fungal cells versus the success of the fungus in mounting compensatory adaptive responses. As each seeks to gain advantage during these skirmishes, the interactions between host and fungal pathogen are complex and dynamic. Nevertheless, simply compromising the physiological robustness of fungal pathogens reduces their ability to evade antifungal immunity, their virulence, and their tolerance against antifungal therapy. In this article I argue that this physiological robustness is based on a 'Resilience Network' which mechanistically links and controls fungal growth, metabolism, stress resistance and drug tolerance. The elasticity of this network probably underlies the phenotypic variability of fungal isolates and the heterogeneity of individual cells within clonal populations. Consequently, I suggest that the definition of the fungal Resilience Network represents an important goal for the future which offers the clear potential to reveal drug targets that compromise drug tolerance and synergise with current antifungal therapies.</p>","PeriodicalId":19931,"journal":{"name":"Parasite Immunology","volume":"45 2","pages":"e12946"},"PeriodicalIF":2.2,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10078341/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9265643","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}

{"title":"C-type lectin receptors in antifungal immunity: Current knowledge and future developments.","authors":"Remi Hatinguais,&nbsp;Janet A Willment,&nbsp;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":"45 2","pages":"e12951"},"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}

{"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":"45 2","pages":"e12960"},"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}