Limits...
Oropharyngeal Candidiasis in HIV Infection: Analysis of Impaired Mucosal Immune Response to Candida albicans in Mice Expressing the HIV-1 Transgene.

de Repentigny L, Goupil M, Jolicoeur P - Pathogens (2015)

Bottom Line: IL-17-producing Th17 cells are of critical importance in host defense against oropharyngeal candidiasis (OPC).Innate phagocytes were quantitatively and functionally intact, and individually dispensable for control of OPC and to prevent systemic dissemination of Candida to deep organs.Therefore, the immunopathogenesis of OPC in the context of HIV infection involves defective T-cell-mediated immunity, failure of crosstalk with innate mucosal immune effector mechanisms, and compensatory cell responses, which limit Candida infection to the oral mucosa and prevent systemic dissemination.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, University of Montreal, C.P. 6128, succursale Centre-Ville, Montreal, PQ H3C 3J7, Canada. louis.de.repentigny@umontreal.ca.

ABSTRACT
IL-17-producing Th17 cells are of critical importance in host defense against oropharyngeal candidiasis (OPC). Speculation about defective Th17 responses to oral C. albicans infection in the context of HIV infection prompted an investigation of innate and adaptive immune responses to Candida albicans in transgenic mice expressing the genome of HIV-1 in immune cells and displaying an AIDS-like disease. Defective IL-17 and IL-22-dependent mucosal responses to C. albicans were found to determine susceptibility to OPC in these transgenic mice. Innate phagocytes were quantitatively and functionally intact, and individually dispensable for control of OPC and to prevent systemic dissemination of Candida to deep organs. CD8+ T-cells recruited to the oral mucosa of the transgenic mice limited the proliferation of C. albicans in these conditions of CD4+ T-cell deficiency. Therefore, the immunopathogenesis of OPC in the context of HIV infection involves defective T-cell-mediated immunity, failure of crosstalk with innate mucosal immune effector mechanisms, and compensatory cell responses, which limit Candida infection to the oral mucosa and prevent systemic dissemination.

No MeSH data available.


Related in: MedlinePlus

Host response to oral Candida albicans. A protective host response to oral C. albicans infection is dependent on dendritic cell-mediated induction of Th17 cell-mediated adaptive immunity, which, by the production of IL-17 upregulates the innate expression of mucosal antimicrobial peptides (β-defensins, calprotectin) by epithelial cells. IL-17 also up-regulates IL-8 and GM-CSF production by epithelial cells, which in turn trigger recruitment of neutrophils to the oral mucosa. Innate-like cell populations, including γδ T-cells, NKT cells, ILCs and nTh17 cells, also produce IL-17 and may participate in the mucosal host response. CLRs, C-type lectin receptors; RNIs, reactive nitrogen intermediates; ROIs, reactive oxygen intermediates; and TLRs, toll-like receptors.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4493482&req=5

pathogens-04-00406-f001: Host response to oral Candida albicans. A protective host response to oral C. albicans infection is dependent on dendritic cell-mediated induction of Th17 cell-mediated adaptive immunity, which, by the production of IL-17 upregulates the innate expression of mucosal antimicrobial peptides (β-defensins, calprotectin) by epithelial cells. IL-17 also up-regulates IL-8 and GM-CSF production by epithelial cells, which in turn trigger recruitment of neutrophils to the oral mucosa. Innate-like cell populations, including γδ T-cells, NKT cells, ILCs and nTh17 cells, also produce IL-17 and may participate in the mucosal host response. CLRs, C-type lectin receptors; RNIs, reactive nitrogen intermediates; ROIs, reactive oxygen intermediates; and TLRs, toll-like receptors.

Mentions: In a landmark investigation, Conti et al., [16] addressed inconsistencies in the prevailing view that the Th1 CD4+ T-cell subset is chiefly responsible for oral mucosal host defense against C. albicans. Previous investigation had shown that IL-12p40-knockout mice are deficient in Th1 cells and susceptible to OPC, but that IFN-γ-knockout mice also have a defective Th1 response and are resistant to OPC [17]. This discrepancy was resolved when it was realized that IL-12p40 is common to the dimeric cytokines IL-12 and IL-23, also composed of the specific components IL-12p35 and IL-23p19, respectively. Conti et al. elegantly demonstrated that IL-23p19-knockout mice are susceptible to OPC and display impaired neutrophil recruitment to the mucosa, while IL-12p35 mice are relatively resistant [16]. They also reported that Th17 signature genes are induced early after oral C. albicans infection of immunocompetent mice, and that mucosal expression of murine β-defensin 3, S100A8 and CCL20 is defective in IL-17RA-knockout mice [16]. These results conclusively showed that IL-17 produced by Th17 cells, and not IL-12 produced by Th1 cells, is critical to a protective host response against OPC, and that neutrophils and mucosal antimicrobial peptides are the primary downstream effector mechanisms of the Th17 anticandidal immune response (Figure 1). In addition to IL-17, IL-22 production by Th17 cells was also shown to contribute to early host protection against C.albicans [16,18,19], which concurred with in vitro evidence that IL-17 and IL-22 cooperatively enhance expression of antimicrobial peptides by oral keratinocytes [20,21,22,23,24] (Figure 1).


Oropharyngeal Candidiasis in HIV Infection: Analysis of Impaired Mucosal Immune Response to Candida albicans in Mice Expressing the HIV-1 Transgene.

de Repentigny L, Goupil M, Jolicoeur P - Pathogens (2015)

Host response to oral Candida albicans. A protective host response to oral C. albicans infection is dependent on dendritic cell-mediated induction of Th17 cell-mediated adaptive immunity, which, by the production of IL-17 upregulates the innate expression of mucosal antimicrobial peptides (β-defensins, calprotectin) by epithelial cells. IL-17 also up-regulates IL-8 and GM-CSF production by epithelial cells, which in turn trigger recruitment of neutrophils to the oral mucosa. Innate-like cell populations, including γδ T-cells, NKT cells, ILCs and nTh17 cells, also produce IL-17 and may participate in the mucosal host response. CLRs, C-type lectin receptors; RNIs, reactive nitrogen intermediates; ROIs, reactive oxygen intermediates; and TLRs, toll-like receptors.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493482&req=5

pathogens-04-00406-f001: Host response to oral Candida albicans. A protective host response to oral C. albicans infection is dependent on dendritic cell-mediated induction of Th17 cell-mediated adaptive immunity, which, by the production of IL-17 upregulates the innate expression of mucosal antimicrobial peptides (β-defensins, calprotectin) by epithelial cells. IL-17 also up-regulates IL-8 and GM-CSF production by epithelial cells, which in turn trigger recruitment of neutrophils to the oral mucosa. Innate-like cell populations, including γδ T-cells, NKT cells, ILCs and nTh17 cells, also produce IL-17 and may participate in the mucosal host response. CLRs, C-type lectin receptors; RNIs, reactive nitrogen intermediates; ROIs, reactive oxygen intermediates; and TLRs, toll-like receptors.
Mentions: In a landmark investigation, Conti et al., [16] addressed inconsistencies in the prevailing view that the Th1 CD4+ T-cell subset is chiefly responsible for oral mucosal host defense against C. albicans. Previous investigation had shown that IL-12p40-knockout mice are deficient in Th1 cells and susceptible to OPC, but that IFN-γ-knockout mice also have a defective Th1 response and are resistant to OPC [17]. This discrepancy was resolved when it was realized that IL-12p40 is common to the dimeric cytokines IL-12 and IL-23, also composed of the specific components IL-12p35 and IL-23p19, respectively. Conti et al. elegantly demonstrated that IL-23p19-knockout mice are susceptible to OPC and display impaired neutrophil recruitment to the mucosa, while IL-12p35 mice are relatively resistant [16]. They also reported that Th17 signature genes are induced early after oral C. albicans infection of immunocompetent mice, and that mucosal expression of murine β-defensin 3, S100A8 and CCL20 is defective in IL-17RA-knockout mice [16]. These results conclusively showed that IL-17 produced by Th17 cells, and not IL-12 produced by Th1 cells, is critical to a protective host response against OPC, and that neutrophils and mucosal antimicrobial peptides are the primary downstream effector mechanisms of the Th17 anticandidal immune response (Figure 1). In addition to IL-17, IL-22 production by Th17 cells was also shown to contribute to early host protection against C.albicans [16,18,19], which concurred with in vitro evidence that IL-17 and IL-22 cooperatively enhance expression of antimicrobial peptides by oral keratinocytes [20,21,22,23,24] (Figure 1).

Bottom Line: IL-17-producing Th17 cells are of critical importance in host defense against oropharyngeal candidiasis (OPC).Innate phagocytes were quantitatively and functionally intact, and individually dispensable for control of OPC and to prevent systemic dissemination of Candida to deep organs.Therefore, the immunopathogenesis of OPC in the context of HIV infection involves defective T-cell-mediated immunity, failure of crosstalk with innate mucosal immune effector mechanisms, and compensatory cell responses, which limit Candida infection to the oral mucosa and prevent systemic dissemination.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology, Infectious Diseases and Immunology, Faculty of Medicine, University of Montreal, C.P. 6128, succursale Centre-Ville, Montreal, PQ H3C 3J7, Canada. louis.de.repentigny@umontreal.ca.

ABSTRACT
IL-17-producing Th17 cells are of critical importance in host defense against oropharyngeal candidiasis (OPC). Speculation about defective Th17 responses to oral C. albicans infection in the context of HIV infection prompted an investigation of innate and adaptive immune responses to Candida albicans in transgenic mice expressing the genome of HIV-1 in immune cells and displaying an AIDS-like disease. Defective IL-17 and IL-22-dependent mucosal responses to C. albicans were found to determine susceptibility to OPC in these transgenic mice. Innate phagocytes were quantitatively and functionally intact, and individually dispensable for control of OPC and to prevent systemic dissemination of Candida to deep organs. CD8+ T-cells recruited to the oral mucosa of the transgenic mice limited the proliferation of C. albicans in these conditions of CD4+ T-cell deficiency. Therefore, the immunopathogenesis of OPC in the context of HIV infection involves defective T-cell-mediated immunity, failure of crosstalk with innate mucosal immune effector mechanisms, and compensatory cell responses, which limit Candida infection to the oral mucosa and prevent systemic dissemination.

No MeSH data available.


Related in: MedlinePlus