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Antigen-Specific Th17 Cells Are Primed by Distinct and Complementary Dendritic Cell Subsets in Oropharyngeal Candidiasis.

Trautwein-Weidner K, Gladiator A, Kirchner FR, Becattini S, Rülicke T, Sallusto F, LeibundGut-Landmann S - PLoS Pathog. (2015)

Bottom Line: The events regulating T cell activation and differentiation toward effector fates in response to fungal invasion in different tissues are poorly understood.This highlights the functional compartmentalization of specific DC subsets in different tissues.These data provide important new insights to our understanding of tissue-specific antifungal immunity.

View Article: PubMed Central - PubMed

Affiliation: Institute of Microbiology, ETH Zürich, Zürich, Switzerland.

ABSTRACT
Candida spp. can cause severe and chronic mucocutaneous and systemic infections in immunocompromised individuals. Protection from mucocutaneous candidiasis depends on T helper cells, in particular those secreting IL-17. The events regulating T cell activation and differentiation toward effector fates in response to fungal invasion in different tissues are poorly understood. Here we generated a Candida-specific TCR transgenic mouse reactive to a novel endogenous antigen that is conserved in multiple distant species of Candida, including the clinically highly relevant C. albicans and C. glabrata. Using TCR transgenic T cells in combination with an experimental model of oropharyngeal candidiasis (OPC) we investigated antigen presentation and Th17 priming by different subsets of dendritic cells (DCs) present in the infected oral mucosa. Candida-derived endogenous antigen accesses the draining lymph nodes and is directly presented by migratory DCs. Tissue-resident Flt3L-dependent DCs and CCR2-dependent monocyte-derived DCs collaborate in antigen presentation and T cell priming during OPC. In contrast, Langerhans cells, which are also present in the oral mucosa and have been shown to prime Th17 cells in the skin, are not required for induction of the Candida-specific T cell response upon oral challenge. This highlights the functional compartmentalization of specific DC subsets in different tissues. These data provide important new insights to our understanding of tissue-specific antifungal immunity.

No MeSH data available.


Related in: MedlinePlus

MHC IIhi CD11c+ migratory DCs present C. albicans-derived antigen in the cervical lymph nodes.(A) Three major populations of CD11c and MHC II positive cells were identified in the cervical lymph nodes of B6 and Ccr7-/- mice on day 2 post-infection: population I (MHC IIhigh CD11c+), population II (MHC II+ CD11chigh) and population III (MHC II+ CD11c+). Representative FACS plots are shown on the left, summary of data from individual mice with mean + SD are shown on the right. (B) CD11b, CD64, CD24 and SIRPα expression in each of the three DC populations in cervical lymph nodes on day 2 post-infection, as defined in (A). Representative FACS plots are shown. (C) The three DC populations defined in (A) were quantified in the cervical lymph nodes of naïve and OPC infected B6 mice. Each symbol represents an individual mouse. Data in (A—C) are representative of at least two independent experiments. (D—E) Mice were infected sublingually with C. albicans and cervical lymph nodes were isolated on day 2 post-infection. The three DC populations defined in (A) were FACS-sorted and co-cultured with CD4+ Hector T cells without adding additional exogenous antigen. Thy1.1+ CD3+ CD4+ TCRVα2+ cells were analyzed for CD69 expression after 1 day (D) and for dilution of the CFSE signal after 4 days (E). Data show representative FACS plots from at least 3 independent experiments.
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ppat.1005164.g004: MHC IIhi CD11c+ migratory DCs present C. albicans-derived antigen in the cervical lymph nodes.(A) Three major populations of CD11c and MHC II positive cells were identified in the cervical lymph nodes of B6 and Ccr7-/- mice on day 2 post-infection: population I (MHC IIhigh CD11c+), population II (MHC II+ CD11chigh) and population III (MHC II+ CD11c+). Representative FACS plots are shown on the left, summary of data from individual mice with mean + SD are shown on the right. (B) CD11b, CD64, CD24 and SIRPα expression in each of the three DC populations in cervical lymph nodes on day 2 post-infection, as defined in (A). Representative FACS plots are shown. (C) The three DC populations defined in (A) were quantified in the cervical lymph nodes of naïve and OPC infected B6 mice. Each symbol represents an individual mouse. Data in (A—C) are representative of at least two independent experiments. (D—E) Mice were infected sublingually with C. albicans and cervical lymph nodes were isolated on day 2 post-infection. The three DC populations defined in (A) were FACS-sorted and co-cultured with CD4+ Hector T cells without adding additional exogenous antigen. Thy1.1+ CD3+ CD4+ TCRVα2+ cells were analyzed for CD69 expression after 1 day (D) and for dilution of the CFSE signal after 4 days (E). Data show representative FACS plots from at least 3 independent experiments.

Mentions: Three major populations of DCs could be identified in cervical lymph nodes according to the expression of MHC II and CD11c: Population I (MHC IIhigh CD11c+), population II (CD11chigh MCH II+), and population III (CD11cint MHC IIint) (Fig 4A). Population I and II expressed CD11b, CD24 and SIRP1α but not CD64, while population III was more heterogeneous for expression of some of these markers (Fig 4B). When compared to the populations found in lymph nodes of Ccr7–/–mice, population II could be identified as lymph node resident DCs and population I as migratory DCs. Population III could also be identified as composed mainly of lymph node resident cells, since the number of CD11cint MHC IIint cells was not affected in Ccr7–/–mice (Fig 4A). During the course of C. albicans infection, populations I and III increased, while population II remained unchanged (Fig 4C).


Antigen-Specific Th17 Cells Are Primed by Distinct and Complementary Dendritic Cell Subsets in Oropharyngeal Candidiasis.

Trautwein-Weidner K, Gladiator A, Kirchner FR, Becattini S, Rülicke T, Sallusto F, LeibundGut-Landmann S - PLoS Pathog. (2015)

MHC IIhi CD11c+ migratory DCs present C. albicans-derived antigen in the cervical lymph nodes.(A) Three major populations of CD11c and MHC II positive cells were identified in the cervical lymph nodes of B6 and Ccr7-/- mice on day 2 post-infection: population I (MHC IIhigh CD11c+), population II (MHC II+ CD11chigh) and population III (MHC II+ CD11c+). Representative FACS plots are shown on the left, summary of data from individual mice with mean + SD are shown on the right. (B) CD11b, CD64, CD24 and SIRPα expression in each of the three DC populations in cervical lymph nodes on day 2 post-infection, as defined in (A). Representative FACS plots are shown. (C) The three DC populations defined in (A) were quantified in the cervical lymph nodes of naïve and OPC infected B6 mice. Each symbol represents an individual mouse. Data in (A—C) are representative of at least two independent experiments. (D—E) Mice were infected sublingually with C. albicans and cervical lymph nodes were isolated on day 2 post-infection. The three DC populations defined in (A) were FACS-sorted and co-cultured with CD4+ Hector T cells without adding additional exogenous antigen. Thy1.1+ CD3+ CD4+ TCRVα2+ cells were analyzed for CD69 expression after 1 day (D) and for dilution of the CFSE signal after 4 days (E). Data show representative FACS plots from at least 3 independent experiments.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4591991&req=5

ppat.1005164.g004: MHC IIhi CD11c+ migratory DCs present C. albicans-derived antigen in the cervical lymph nodes.(A) Three major populations of CD11c and MHC II positive cells were identified in the cervical lymph nodes of B6 and Ccr7-/- mice on day 2 post-infection: population I (MHC IIhigh CD11c+), population II (MHC II+ CD11chigh) and population III (MHC II+ CD11c+). Representative FACS plots are shown on the left, summary of data from individual mice with mean + SD are shown on the right. (B) CD11b, CD64, CD24 and SIRPα expression in each of the three DC populations in cervical lymph nodes on day 2 post-infection, as defined in (A). Representative FACS plots are shown. (C) The three DC populations defined in (A) were quantified in the cervical lymph nodes of naïve and OPC infected B6 mice. Each symbol represents an individual mouse. Data in (A—C) are representative of at least two independent experiments. (D—E) Mice were infected sublingually with C. albicans and cervical lymph nodes were isolated on day 2 post-infection. The three DC populations defined in (A) were FACS-sorted and co-cultured with CD4+ Hector T cells without adding additional exogenous antigen. Thy1.1+ CD3+ CD4+ TCRVα2+ cells were analyzed for CD69 expression after 1 day (D) and for dilution of the CFSE signal after 4 days (E). Data show representative FACS plots from at least 3 independent experiments.
Mentions: Three major populations of DCs could be identified in cervical lymph nodes according to the expression of MHC II and CD11c: Population I (MHC IIhigh CD11c+), population II (CD11chigh MCH II+), and population III (CD11cint MHC IIint) (Fig 4A). Population I and II expressed CD11b, CD24 and SIRP1α but not CD64, while population III was more heterogeneous for expression of some of these markers (Fig 4B). When compared to the populations found in lymph nodes of Ccr7–/–mice, population II could be identified as lymph node resident DCs and population I as migratory DCs. Population III could also be identified as composed mainly of lymph node resident cells, since the number of CD11cint MHC IIint cells was not affected in Ccr7–/–mice (Fig 4A). During the course of C. albicans infection, populations I and III increased, while population II remained unchanged (Fig 4C).

Bottom Line: The events regulating T cell activation and differentiation toward effector fates in response to fungal invasion in different tissues are poorly understood.This highlights the functional compartmentalization of specific DC subsets in different tissues.These data provide important new insights to our understanding of tissue-specific antifungal immunity.

View Article: PubMed Central - PubMed

Affiliation: Institute of Microbiology, ETH Zürich, Zürich, Switzerland.

ABSTRACT
Candida spp. can cause severe and chronic mucocutaneous and systemic infections in immunocompromised individuals. Protection from mucocutaneous candidiasis depends on T helper cells, in particular those secreting IL-17. The events regulating T cell activation and differentiation toward effector fates in response to fungal invasion in different tissues are poorly understood. Here we generated a Candida-specific TCR transgenic mouse reactive to a novel endogenous antigen that is conserved in multiple distant species of Candida, including the clinically highly relevant C. albicans and C. glabrata. Using TCR transgenic T cells in combination with an experimental model of oropharyngeal candidiasis (OPC) we investigated antigen presentation and Th17 priming by different subsets of dendritic cells (DCs) present in the infected oral mucosa. Candida-derived endogenous antigen accesses the draining lymph nodes and is directly presented by migratory DCs. Tissue-resident Flt3L-dependent DCs and CCR2-dependent monocyte-derived DCs collaborate in antigen presentation and T cell priming during OPC. In contrast, Langerhans cells, which are also present in the oral mucosa and have been shown to prime Th17 cells in the skin, are not required for induction of the Candida-specific T cell response upon oral challenge. This highlights the functional compartmentalization of specific DC subsets in different tissues. These data provide important new insights to our understanding of tissue-specific antifungal immunity.

No MeSH data available.


Related in: MedlinePlus