Oral-resident natural Th17 cells and γδ T cells control opportunistic <i>Candida albicans</i> infections

Conti, Heather R.; Peterson, Alanna; Brane, Lucas; Huppler, Anna R.; Hernández-Santos, Nydiaris; Whibley, Natasha; Garg, Abhishek V.; Simpson-Abelson, Michelle R.; Gibson, Gregory A.; Mamo, Anna J.; Osborne, Lisa C.; Bishu, Shrinivas; Ghilardi, Nico; Siebenlist, Ulrich; Watkins, Simon C.; Artis, David; McGeachy, Mandy J.; Gaffen, Sarah L.

doi:10.1084/jem.20130877

Cited by 224 publications

(277 citation statements)

References 56 publications

(130 reference statements)

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“…Tissue-resident gdT17 cells have been described in the gut lamina propria, in the dermis, in entheseal tissue (21,(47)(48)(49), and are likely present in a variety of other epithelial barriers. Their physiological role in these niches is not entirely clear.…”

Section: Discussionmentioning

confidence: 99%

IL-1β and IL-23 Promote Extrathymic Commitment of CD27+CD122− γδ T Cells to γδT17 Cells

Muschaweckh

Petermann

Korn

2017

The Journal of Immunology

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γδT17 cells are a subset of γδ T cells committed to IL-17 production and are characterized by the expression of IL-23R and CCR6 and lack of CD27 expression. γδT17 cells are believed to arise within a narrow time window during prenatal thymic development. In agreement with this concept, we show in this study that adult Rag1−/− recipient mice of Il23rgfp/+ (IL-23R reporter) bone marrow selectively lack IL-23R+ γδT17 cells. Despite their absence in secondary lymphoid tissues during homeostasis, γδT17 cells emerge in bone marrow chimeric mice upon induction of skin inflammation by topical treatment with imiquimod cream (Aldara). We demonstrate that IL-1β and IL-23 together are able to promote the development of bona fide γδT17 cells from peripheral CD122−IL-23R− γδ T cells, whereas CD122+ γδ T cells fail to convert into γδT17 cells and remain stable IFN-γ producers (γδT1 cells). IL-23 is instrumental in expanding extrathymically generated γδT17 cells. In particular, TCR-Vγ4+ chain–expressing CD122−IL-23R− γδ T cells are induced to express IL-23R and IL-17 outside the thymus during skin inflammation. In contrast, TCR-Vγ1+ γδ T cells largely resist this process because prior TCR engagement in the thymus has initiated their commitment to the γδT1 lineage. In summary, our data reveal that the peripheral pool of γδ T cells retains a considerable degree of plasticity because it harbors “naive” precursors, which can be induced to produce IL-17 and replenish peripheral niches that are usually occupied by thymus-derived γδT17 cells.

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Section: Discussionmentioning

confidence: 99%

IL-1β and IL-23 Promote Extrathymic Commitment of CD27+CD122− γδ T Cells to γδT17 Cells

Muschaweckh

Petermann

Korn

2017

The Journal of Immunology

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“…γδ 17 cells are observed in lungs after systemic C. albicans infection, and both Il17 −/− and Tcrd −/− mice are defective in neutrophil recruitment and fungal clearance 84. Interleukin‐17 is produced in tongue‐resident γδ T cells as well as CD3 + CD4 + CD44 hi TCR‐ β + CCR6 + natural Th17 cells within 1–2 days after oral C. albicans infection 85. As IL‐17 production in γδ T cells is found at the early stage after infection, γδ 17 cells are suggested to play an important role in early host defence before establishment of acquired immunity.…”

Section: γδ17 Cells In Pathogen Clearancementioning

confidence: 99%

Interleukin‐17‐producing γδ T (γδ17) cells in inflammatory diseases

Akitsu

Iwakura

2018

Immunology

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SummaryInterleukin‐17 (IL‐17) is a pro‐inflammatory cytokine and is involved in the development of many diseases. Recent studies have revealed that IL‐17‐producing γδ T cells (γδ17 cells) in addition to IL‐17‐producing CD4+ T cells [T helper type 17 (Th17) cells] are often the main producers of IL‐17 in mouse models of inflammatory diseases. γδ T cells are functionally committed during intra‐thymic differentiation. γδ thymocytes capable of producing IL‐17, which express the transcription factor retinoic‐acid‐receptor‐related orphan receptor γt and the signature cytokine receptor IL‐23R, leave the thymus, and produce IL‐17 rapidly by the stimulation with IL‐1β and IL‐23 in the periphery. Therefore, γδ17 cells play important roles in the early phase of host defence against pathogens and in inflammatory diseases. γδ T cells that can produce IL‐17 are also increased in the skin of patients with psoriasis and in peripheral blood of patients with ankylosing sclerosis. Indeed, the therapy targeting IL‐17 has been approved or is in clinical trials, and proved to be very efficient to treat psoriasis, psoriatic arthritis and ankylosing sclerosis. In this review, we discuss recent knowledge about the pathophysiological function of γδ17 cells in infection and inflammatory diseases and therapeutic advances targeting IL‐17.

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“…Host defense against C. albicans requires the IL-17 pathway of cells and cytokines (5)(6)(7)(8). IL-17 is an inflammatory cytokine released by a subset of CD4 + T cells (Th17 cells), some CD8 + T cells, NK cells, NK T cells, and innate lymphoid cells (9)(10)(11).…”

mentioning

confidence: 99%

“…However, the mechanisms by which C. albicans stimulates Vd1 T cells are poorly understood. Murine gd T cells expressing TLR2 and dectin-1, which bind to b-glucans present in cells walls of fungi, are implicated in responses to C. albicans (8,(18)(19)(20). Murine gd T cells can also release IL-17A and the Th17-associated cytokines, IL-17F, IL-21, and IL-22, in response to treatment with IL-1 and IL-23, or IL-18 and IL-23 in the absence of TCR stimulation (21,22).…”

mentioning

confidence: 99%

Candida albicansStimulates IL-23 Release by Human Dendritic Cells and Downstream IL-17 Secretion by Vδ1 T Cells

Maher

Dunne

Comerford

et al. 2015

The Journal of Immunology

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γδ T cells expressing the Vδ1 TCR are expanded in patients with HIV infection. We show in this article that circulating Vδ1 T cell numbers are particularly high in patients with HIV and candidiasis, and that these cells expand and produce IL-17 in response to Candida albicans in vitro. Although C. albicans could directly stimulate IL-17 production by a subset of Vδ1 T cells, fungus-treated dendritic cells (DCs) were required to expand C. albicans–responsive Vδ1 T cells to generate sufficient numbers of cells to release IL-17 at levels detectable by ELISA. C. albicans induced the release of IL-1β, IL-6, and IL-23 by DCs, but addition of these cytokines or supernatants of C. albicans–treated DCs to Vδ1 T cells was not sufficient to induce proliferation. We found that direct contact with DCs was required for Vδ1 T cell proliferation, whereas IL-23R–blocking studies showed that IL-23 was required for optimal C. albicans–induced IL-17 production. Because IL-17 affords protection against both HIV and C. albicans, and because Vδ1 T cells are not depleted by HIV, these cells are likely to be an important source of IL-17 in HIV-infected patients with candidiasis, in whom CD4+ Th17 responses are impaired. These data show that C. albicans stimulates proliferation and IL-17 production by Vδ1 T cells by a mechanism that involves IL-23 release by DCs.

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Oral-resident natural Th17 cells and γδ T cells control opportunistic Candida albicans infections

Abstract: Conti et al. show that IL-17 is produced by tongue-resident populations of γδ T cells and nTh17 cells in response to oropharyngeal candidiasis in mice.

Cited by 224 publications

References 56 publications

IL-1β and IL-23 Promote Extrathymic Commitment of CD27+CD122− γδ T Cells to γδT17 Cells

IL-1β and IL-23 Promote Extrathymic Commitment of CD27+CD122− γδ T Cells to γδT17 Cells

Interleukin‐17‐producing γδ T (γδ17) cells in inflammatory diseases

Candida albicansStimulates IL-23 Release by Human Dendritic Cells and Downstream IL-17 Secretion by Vδ1 T Cells

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