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F A Schonherr - One of the best experts on this subject based on the ideXlab platform.
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the intraspecies diversity of c albicans triggers qualitatively and temporally distinct host Responses that determine the balance between commensalism and pathogenicity
Mucosal Immunology, 2017Co-Authors: Florian Sparber, A Gladiator, F A Schonherr, Florian R Kirchner, Eva Guiducci, K Trautweinweidner, Natacha Sertour, U Hetzel, Norman PavelkaAbstract:The host immune status is critical for preventing opportunistic infections with Candida albicans. Whether the natural fungal diversity that exists between C. albicans isolates also influences disease development remains unclear. Here, we used an experimental model of oral infection to probe the host Response to diverse C. albicans isolates in vivo and found dramatic differences in their ability to persist in the oral mucosa, which inversely correlated with the degree and kinetics of immune activation in the host. Strikingly, the requirement of interleukin (IL)-17 signaling for fungal control was conserved between isolates, including isolates with delayed induction of IL-17. This underscores the relevance of IL-17 immunity in mucosal defense against C. albicans. In contrast, the accumulation of Neutrophils and induction of inflammation in the infected tissue was strictly strain dependent. The dichotomy of the inflammatory Neutrophil Response was linked to the capacity of fungal strains to cause cellular damage and release of alarmins from the epithelium. The epithelium thus translates differences in the fungus into qualitatively distinct host Responses. Altogether, this study provides a comprehensive understanding of the antifungal Response in the oral mucosa and demonstrates the relevance of evaluating intraspecies differences for the outcome of fungal–host interactions in vivo.
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The intraspecies diversity of C. albicans triggers qualitatively and temporally distinct host Responses that determine the balance between commensalism and pathogenicity
Mucosal Immunology, 2017Co-Authors: F A Schonherr, K Trautwein-weidner, A Gladiator, Florian R Kirchner, Eva Guiducci, Natacha Sertour, U Hetzel, Norman Pavelka, F Sparber, C D'enfertAbstract:The host immune status is critical for preventing opportunistic infections with Candida albicans. Whether the natural fungal diversity that exists between C. albicans isolates also influences disease development remains unclear. Here, we used an experimental model of oral infection to probe the host Response to diverse C. albicans isolates in vivo and found dramatic differences in their ability to persist in the oral mucosa, which inversely correlated with the degree and kinetics of immune activation in the host. Strikingly, the requirement of interleukin (IL)-17 signaling for fungal control was conserved between isolates, including isolates with delayed induction of IL-17. This underscores the relevance of IL-17 immunity in mucosal defense against C. albicans. In contrast, the accumulation of Neutrophils and induction of inflammation in the infected tissue was strictly strain dependent. The dichotomy of the inflammatory Neutrophil Response was linked to the capacity of fungal strains to cause cellular damage and release of alarmins from the epithelium. The epithelium thus translates differences in the fungus into qualitatively distinct host Responses. Altogether, this study provides a comprehensive understanding of the antifungal Response in the oral mucosa and demonstrates the relevance of evaluating intraspecies differences for the outcome of fungal-host interactions in vivo.Mucosal Immunology advance online publication 8 February 2017. doi:10.1038/mi.2017.2.
Norman Pavelka - One of the best experts on this subject based on the ideXlab platform.
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the intraspecies diversity of c albicans triggers qualitatively and temporally distinct host Responses that determine the balance between commensalism and pathogenicity
Mucosal Immunology, 2017Co-Authors: Florian Sparber, A Gladiator, F A Schonherr, Florian R Kirchner, Eva Guiducci, K Trautweinweidner, Natacha Sertour, U Hetzel, Norman PavelkaAbstract:The host immune status is critical for preventing opportunistic infections with Candida albicans. Whether the natural fungal diversity that exists between C. albicans isolates also influences disease development remains unclear. Here, we used an experimental model of oral infection to probe the host Response to diverse C. albicans isolates in vivo and found dramatic differences in their ability to persist in the oral mucosa, which inversely correlated with the degree and kinetics of immune activation in the host. Strikingly, the requirement of interleukin (IL)-17 signaling for fungal control was conserved between isolates, including isolates with delayed induction of IL-17. This underscores the relevance of IL-17 immunity in mucosal defense against C. albicans. In contrast, the accumulation of Neutrophils and induction of inflammation in the infected tissue was strictly strain dependent. The dichotomy of the inflammatory Neutrophil Response was linked to the capacity of fungal strains to cause cellular damage and release of alarmins from the epithelium. The epithelium thus translates differences in the fungus into qualitatively distinct host Responses. Altogether, this study provides a comprehensive understanding of the antifungal Response in the oral mucosa and demonstrates the relevance of evaluating intraspecies differences for the outcome of fungal–host interactions in vivo.
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The intraspecies diversity of C. albicans triggers qualitatively and temporally distinct host Responses that determine the balance between commensalism and pathogenicity
Mucosal Immunology, 2017Co-Authors: F A Schonherr, K Trautwein-weidner, A Gladiator, Florian R Kirchner, Eva Guiducci, Natacha Sertour, U Hetzel, Norman Pavelka, F Sparber, C D'enfertAbstract:The host immune status is critical for preventing opportunistic infections with Candida albicans. Whether the natural fungal diversity that exists between C. albicans isolates also influences disease development remains unclear. Here, we used an experimental model of oral infection to probe the host Response to diverse C. albicans isolates in vivo and found dramatic differences in their ability to persist in the oral mucosa, which inversely correlated with the degree and kinetics of immune activation in the host. Strikingly, the requirement of interleukin (IL)-17 signaling for fungal control was conserved between isolates, including isolates with delayed induction of IL-17. This underscores the relevance of IL-17 immunity in mucosal defense against C. albicans. In contrast, the accumulation of Neutrophils and induction of inflammation in the infected tissue was strictly strain dependent. The dichotomy of the inflammatory Neutrophil Response was linked to the capacity of fungal strains to cause cellular damage and release of alarmins from the epithelium. The epithelium thus translates differences in the fungus into qualitatively distinct host Responses. Altogether, this study provides a comprehensive understanding of the antifungal Response in the oral mucosa and demonstrates the relevance of evaluating intraspecies differences for the outcome of fungal-host interactions in vivo.Mucosal Immunology advance online publication 8 February 2017. doi:10.1038/mi.2017.2.
A Gladiator - One of the best experts on this subject based on the ideXlab platform.
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The intraspecies diversity of C. albicans triggers qualitatively and temporally distinct host Responses that determine the balance between commensalism and pathogenicity
Mucosal Immunology, 2017Co-Authors: F A Schonherr, K Trautwein-weidner, A Gladiator, Florian R Kirchner, Eva Guiducci, Natacha Sertour, U Hetzel, Norman Pavelka, F Sparber, C D'enfertAbstract:The host immune status is critical for preventing opportunistic infections with Candida albicans. Whether the natural fungal diversity that exists between C. albicans isolates also influences disease development remains unclear. Here, we used an experimental model of oral infection to probe the host Response to diverse C. albicans isolates in vivo and found dramatic differences in their ability to persist in the oral mucosa, which inversely correlated with the degree and kinetics of immune activation in the host. Strikingly, the requirement of interleukin (IL)-17 signaling for fungal control was conserved between isolates, including isolates with delayed induction of IL-17. This underscores the relevance of IL-17 immunity in mucosal defense against C. albicans. In contrast, the accumulation of Neutrophils and induction of inflammation in the infected tissue was strictly strain dependent. The dichotomy of the inflammatory Neutrophil Response was linked to the capacity of fungal strains to cause cellular damage and release of alarmins from the epithelium. The epithelium thus translates differences in the fungus into qualitatively distinct host Responses. Altogether, this study provides a comprehensive understanding of the antifungal Response in the oral mucosa and demonstrates the relevance of evaluating intraspecies differences for the outcome of fungal-host interactions in vivo.Mucosal Immunology advance online publication 8 February 2017. doi:10.1038/mi.2017.2.
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the intraspecies diversity of c albicans triggers qualitatively and temporally distinct host Responses that determine the balance between commensalism and pathogenicity
Mucosal Immunology, 2017Co-Authors: Florian Sparber, A Gladiator, F A Schonherr, Florian R Kirchner, Eva Guiducci, K Trautweinweidner, Natacha Sertour, U Hetzel, Norman PavelkaAbstract:The host immune status is critical for preventing opportunistic infections with Candida albicans. Whether the natural fungal diversity that exists between C. albicans isolates also influences disease development remains unclear. Here, we used an experimental model of oral infection to probe the host Response to diverse C. albicans isolates in vivo and found dramatic differences in their ability to persist in the oral mucosa, which inversely correlated with the degree and kinetics of immune activation in the host. Strikingly, the requirement of interleukin (IL)-17 signaling for fungal control was conserved between isolates, including isolates with delayed induction of IL-17. This underscores the relevance of IL-17 immunity in mucosal defense against C. albicans. In contrast, the accumulation of Neutrophils and induction of inflammation in the infected tissue was strictly strain dependent. The dichotomy of the inflammatory Neutrophil Response was linked to the capacity of fungal strains to cause cellular damage and release of alarmins from the epithelium. The epithelium thus translates differences in the fungus into qualitatively distinct host Responses. Altogether, this study provides a comprehensive understanding of the antifungal Response in the oral mucosa and demonstrates the relevance of evaluating intraspecies differences for the outcome of fungal–host interactions in vivo.
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IL-17-mediated antifungal defense in the oral mucosa is independent of Neutrophils
Mucosal Immunology, 2015Co-Authors: K Trautwein-weidner, A Gladiator, P Diethelm, S Leibundgut-landmannAbstract:Interleukin-17 (IL-17)-mediated immunity has emerged as a crucial host defense mechanism against Candida albicans infections in mucosal tissues and the skin. The precise mechanism by which the IL-17 pathway prevents fungal outgrowth has not been clarified. Neutrophils are critical for limiting fungal dissemination and IL-17 is generally thought to act by regulating Neutrophil mobilization and trafficking to the site of infection. Using a mouse model of oropharyngeal candidiasis (OPC), we found that strikingly the IL-17 pathway is not required for the Neutrophil Response to C. albicans . Mice deficient for the IL-17 receptor subunits IL-17 receptor A (IL-17RA) or IL-17RC or mice depleted of IL-17A and IL-17F exhibited a normal granulocyte colony-stimulating factor (G-CSF) and CXC-chemokine Response and displayed no defect in Neutrophil recruitment or function. Instead, the inability of these mice to clear the fungus was associated with a selective defect in the induction of antimicrobial peptides (AMPs) in the epithelium that resulted in persistent fungal colonization. Importantly, this antifungal mechanism of IL-17A and IL-17F did not extend to the closely related family member IL-17C. Together, these data uncouple IL-17-dependent effector mechanisms from the Neutrophil Response and reveal a compartmentalization of the antifungal defense in the oral mucosa providing a new understanding of IL-17-mediated mucosal immunity against C. albicans .
Paul L. Fidel - One of the best experts on this subject based on the ideXlab platform.
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the acute Neutrophil Response mediated by s100 alarmins during vaginal candida infections is independent of the th17 pathway
PLOS ONE, 2012Co-Authors: Junko Yano, Jay K Kolls, Kyle I Happel, Floyd L Wormley, Karen L Wozniak, Paul L. FidelAbstract:Vulvovaginal candidiasis (VVC) caused by Candida albicans affects a significant number of women during their reproductive ages. Clinical observations revealed that a robust vaginal polymorphonuclear Neutrophil (PMN) migration occurs in susceptible women, promoting pathological inflammation without affecting fungal burden. Evidence to date in the mouse model suggests that a similar acute PMN migration into the vagina is mediated by chemotactic S100A8 and S100A9 alarmins produced by vaginal epithelial cells in Response to Candida. Based on the putative role for the Th17 Response in mucosal candidiasis as well as S100 alarmin induction, this study aimed to determine whether the Th17 pathway plays a role in the S100 alarmin-mediated acute inflammation during VVC using the experimental mouse model. For this, IL-23p19−/−, IL-17RA−/− and IL-22−/− mice were intravaginally inoculated with Candida, and vaginal lavage fluids were evaluated for fungal burden, PMN infiltration, the presence of S100 alarmins and inflammatory cytokines and chemokines. Compared to wild-type mice, the cytokine-deficient mice showed comparative levels of vaginal fungal burden and PMN infiltration following inoculation. Likewise, inoculated mice of all strains with substantial PMN infiltration exhibited elevated levels of vaginal S100 alarmins in both vaginal epithelia and secretions in the vaginal lumen. Finally, cytokine analyses of vaginal lavage fluid from inoculated mice revealed equivalent expression profiles irrespective of the Th17 cytokine status or PMN Response. These data suggest that the vaginal S100 alarmin Response to Candida does not require the cells or cytokines of the Th17 lineage, and therefore, the immunopathogenic inflammatory Response during VVC occurs independently of the Th17-pathway.
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epithelial cell derived s100 calcium binding proteins as key mediators in the hallmark acute Neutrophil Response during candida vaginitis
Infection and Immunity, 2010Co-Authors: Junko Yano, Melissa M Barousse, E A Lilly, Paul L. FidelAbstract:Vulvovaginal candidiasis (VVC), caused by Candida species, is a significant problem in women of childbearing age. Similar to clinical observations, a robust vaginal polymorphonuclear Neutrophil (PMN) migration occurs in a subset of mice without affecting vaginal fungal burden. We hypothesize that the vaginal PMN infiltrate and accompanying inflammation are not protective but instead are responsible for the symptoms of infection. The purpose of this study was to identify the signal(s) associated with the PMN Response in the established mouse model. Vaginal lavage fluid from inoculated mice were categorized base on PMN counts, evaluated for PMN chemotactic activity and analyzed by SDS-PAGE and mass spectrometry (MS) for unique protein identification. The lavage fluid from inoculated mice with high, but not low, PMN levels showed increased chemotactic activity. Likewise, SDS-PAGE of lavage fluid with high PMN levels showed distinct protein patterns. MS revealed that bands at 6 and 14 kDa matched the PMN chemotactic calcium-binding proteins (CBPs), S100A8 and S100A9, respectively. The presence of the CBPs in lavage fluid was confirmed by Western blots and enzyme-linked immunosorbent assay. Vaginal tissues and epithelial cells from inoculated mice with high PMN levels stained more intensely and exhibited increased mRNA transcripts for both proteins compared to those in mice with low PMN levels. Subsequent antibody neutralization showed significant abrogation of the chemotactic activity when the lavage fluid was treated with anti-S100A8, but not anti-S100A9, antibodies. These results reveal that the PMN chemotactic CBP S100A8 and S100A9 are produced by vaginal epithelial cells following interaction with Candida and that S100A8 is a strong candidate responsible for the robust PMN migration during experimental VVC.
Leo Koenderman - One of the best experts on this subject based on the ideXlab platform.
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a systemic Neutrophil Response precedes robust cd8 t cell activation during natural respiratory syncytial virus infection in infants
Journal of Virology, 2010Co-Authors: Michael V Lukens, Frank E J Coenjaerts, Nicolaas J G Jansen, Vera M Kamp, Jan L L Kimpen, John W A Rossen, Laurien H Ulfman, Carline E Tacke, Marco C Viveen, Leo KoendermanAbstract:Viral infections are characterized by a dynamic interplay between the pathogen and defensive innate and adaptive immune Responses of the host (35, 38). Upon infection, virus-specific structural components are recognized by pattern recognition receptors of the host, which triggers a mechanism aimed at the suppression of virus replication and eventually virus elimination. Each virus has a characteristic signature of triggering innate immune receptors and methods to counteract immune Responses of the host, which ultimately results in an immune Response tailored to the particular properties of the infecting virus (6). Most insights into the sequence of events occurring during viral infections have been obtained from animal experiments, where the immunological control of viral infections can be studied in detail. In many murine models, the crucial role of CD8+ T cells in complete elimination of the virus during acute infections has been well established (9, 20, 27). However, both virus-induced damage and immune pathology might contribute to the disease, depending on the type of viral infection and/or the intensity of the innate and adaptive immune Responses triggered (10, 20, 37, 41, 49, 60). Primary infections with respiratory syncytial virus (RSV) can cause severe bronchiolitis and pneumonia in infants (24). For RSV, the mouse is not a good model to study primary disease because the virus replicates poorly in murine cells. Hence, to obtain insight into the mechanism of disease caused by RSV, infection studies in humans or nonhuman primate models are needed. We and others have shown that RSV infection causes a strong influx of Neutrophils into the airways (15, 25, 48). In addition, we have recently shown that substantial virus-specific CD8+ T-cell Responses can be elicited in infants with severe RSV infections (25). However, it is still a controversial issue whether the severe manifestations of lower respiratory tract disease are caused directly by the virus or by innate and/or adaptive immune Responses triggered by RSV (8, 20, 31, 57). In our previous work, we found no relation between the severity of disease and the number of virus-specific CD8+ T cells in peripheral blood (25). Moreover, a direct role of the viral load or different viral strains in disease severity has not been established convincingly (11, 59). Data on the development of primary T-cell Responses in infants (<6 months old) during acute viral infections and after vaccinations are sparse. It is generally accepted that the infant immune system is immature and less effective than that of older children or adults. This has been shown by lower activation and/or Th2-polarized adaptive immune Responses (1, 2, 58). For RSV-induced disease, it has been suggested that a Th2-biased immune Response might be correlated with disease (39, 45, 50), but this idea has been challenged by others (4, 7, 12). Currently, there is no RSV vaccine, and the only preventive treatment available is a humanized neutralizing antibody specific for the fusion protein of RSV that is administered to high-risk groups and is effective in about 60% of children (29). Immune-suppressive or antiviral treatments during severe RSV disease have marginal to no effect (3, 23, 55). Insights into the kinetics of the viral load and disease course in relation to activation of the innate and adaptive immune Response will shed light on factors that are attributed to severe RSV-induced disease and will possibly provide leads for the development of curative treatment. We therefore monitored the dynamics of these parameters in infants admitted to the pediatric intensive care unit (ICU) with severe primary RSV infections. During primary RSV infection, the peak values of the viral load and disease severity were followed by the exhaustion of the peripheral blood Neutrophil pool, indicating a strong innate immune Response closely associated with the peak of disease. We further showed that this natural respiratory infection elicited a strong primary CD8+ T-cell Response in the very young patients (<3 months). This T-cell Response was undetectable at the moment of hospitalization, when the infants were severely ill, and peaked at convalescence. Therefore, severe primary RSV disease does not seem to be caused by inadequate or exaggerated T-cell Responses but is most likely initiated by viral damage followed by intense innate immune processes.