Dectin-1 isoforms contribute to distinct Th1/Th17 cell activation in mucosal candidiasis

Abstract

The recognition of b-glucans by dectin-1 has been shown to mediate cell activation, cytokine production and a variety of antifungal responses. Here, we report that the functional activity of dectin-1 in mucosal immunity to Candida albicans is influenced by the genetic background of the host. Dectin-1 was required for the proper control of gastrointestinal and vaginal candidiasis in C57BL/6, but not BALB/c mice; in fact, the latter showed increased resistance in the absence of dectin-1. The susceptibility of dectin-1-deficient C57BL/6 mice to infection was associated with defects in IL-17A and aryl hydrocarbon receptor-dependent IL-22 production and in adaptive Th1 responses. In contrast, the resistance of dectin-1-deficient BALB/c mice was associated with increased IL-17A and IL-22 production and the skewing towards Th1/Treg immune responses that provide immunological memory. Disparate canonical/ noncanonical NF-kB signaling pathways downstream of dectin-1 were activated in the two different mouse strains. Thus, the net activity of dectin-1 in antifungal mucosal immunity is dependent on the host's genetic background, which affects both the innate cytokine production and the adaptive Th1/Th17 cell activation upon dectin-1 signaling.

Decidual stromal cells recruit Th17 cells into decidua to promote proliferation and invasion of human trophoblast cells by secreting IL-17

“…The change in Th17 cells is similar to that observed in natural Treg cells during human pregnancy, 6,22,23 and there is a reciprocal interaction between Treg cells and Th17 cells. 9 Therefore, we hypothesized that Th17 cells may act in concert with Treg cells to maintain maternal-fetal tolerance. Th17 cells impair Th1 response in the gut, 15 and whether Th17 cells impair Th1 response in coordination with Treg cells at the maternal/fetal interface remains to be elucidated.…”

“…[7][8][9] As a key cytokine produced by Th17 cells, IL-17 and other cytokines are involved in certain inflammatory and autoimmune diseases, including acute coronary syndrome, 10 multiple sclerosis, 11 inflammatory bowel diseases 12 and psoriasis. 13 However, Th17 cells might also have regulatory and protective roles in the gut and liver.…”

Caspases as the Key Effectors of Inflammatory Responses Against Bacterial Infection

“…Activated dectin-1 induces the expression of various genes through NF-jB, leading to the production of cytokines that initiate the T helper 1 (Th1) or Th17 responses (Carvalho et al 2012;Gow et al 2007). In addition, dectin-1 contributes to IL-1b production against fungal or mycobacterial infection.…”

Immune Response and Candidal Colonisation in Denture Associated Stomatitis

“…It is now generally accepted, that Th1/Th17-type responses are protective against candidosis [17,18], whilst a Th2 response is non-protective [19]. Interestingly, Treg cells are positively associated with elevated Th17 cells in the skin [16]. Tregs can secrete TGFβ1 which is a critical cytokine for Th17 development and can also suppress Th1 cells and dendritic cell function, resulting in immune suppression [20,21].…”

“…All these cells are able to produce cytokines and generate a tissue environment that can either promote or suppress the immune mechanisms involved in controlling Candida. CD4 + T cells are the most influential host immune cells in this respect, and dictate immunity against Candida by secreting cytokines, such as those associated with Th1 (IFNγ and IL-2), Th17 (IL-17a and IL-22) and Treg cells (IL-10 and TGF-β1) [16]. It is now generally accepted, that Th1/Th17-type responses are protective against candidosis [17,18], whilst a Th2 response is non-protective [19].…”