Host responses to Candida albicans: Th17 cells and mucosal candidiasis

Abstract

Candida albicans causes mucosal and disseminated candidiasis, which represent serious problems for the rapidly expanding immunocompromised population. Until recently, Th1-mediated immunity was thought to confer the primary protection, particularly for oral candidiasis. However, emerging data indicate that the newly-defined Th17 compartment appears to play the predominant role in mucosal candidiasis.

Figure 1. T-helper cell differentiation

(A) Upon activation by signaling through the T-cell receptor and co-stimulatory molecules, naïve CD4+ Th precursor (Thp) cells can differentiate into three lineages of effector T helper (Th) cells, Th1, Th2 or Th17 cells depending on the local cytokine milieu. Each subset produces different cytokines that mediate distinct effector mechanisms. IL-12 is an important cytokine for the development of Th1 cells, which produce IFN-γ, through which they promote CMI and protection against intracellular pathogens. IL-4 promotes the expansion of Th2 cells, which produce IL-4, IL-5 and IL-13 and are important in allergy and protection against helminthes. On the other hand, Th17 cells develop in the presence of IL-1, IL-6 and TGF-β, while IL-23 is important for the expansion, maintenance and function of Th17 cells. Th17 cells are implicated in autoimmunity and protect against extracellular microbes, including C. albicans, a role that was erroneously ascribed to Th1 cells in many instances. The transcription factor STAT3 is very important at many steps exclusively along the Th17-development pathway. (B) C. albicans is recognized, taken up by antigen presenting cells (APCs), such as macrophages and dendritic cells (DCs), processed and presented to T cells. A balanced response to Candida includes the cooperation of many PRRs. Upon recognition of C. albicans yeast and hyphae, CLRs (dectin-1, dectin-2, and the MR) and the NLRP3 inflammasome are important in the generation of a protective Th17-response through the induction of IL-1β, IL-6, and TGF-β.

Figure 1. T-helper cell differentiation

(A) Upon activation by signaling through the T-cell receptor and co-stimulatory molecules, naïve CD4+ Th precursor (Thp) cells can differentiate into three lineages of effector T helper (Th) cells, Th1, Th2 or Th17 cells depending on the local cytokine milieu. Each subset produces different cytokines that mediate distinct effector mechanisms. IL-12 is an important cytokine for the development of Th1 cells, which produce IFN-γ, through which they promote CMI and protection against intracellular pathogens. IL-4 promotes the expansion of Th2 cells, which produce IL-4, IL-5 and IL-13 and are important in allergy and protection against helminthes. On the other hand, Th17 cells develop in the presence of IL-1, IL-6 and TGF-β, while IL-23 is important for the expansion, maintenance and function of Th17 cells. Th17 cells are implicated in autoimmunity and protect against extracellular microbes, including C. albicans, a role that was erroneously ascribed to Th1 cells in many instances. The transcription factor STAT3 is very important at many steps exclusively along the Th17-development pathway. (B) C. albicans is recognized, taken up by antigen presenting cells (APCs), such as macrophages and dendritic cells (DCs), processed and presented to T cells. A balanced response to Candida includes the cooperation of many PRRs. Upon recognition of C. albicans yeast and hyphae, CLRs (dectin-1, dectin-2, and the MR) and the NLRP3 inflammasome are important in the generation of a protective Th17-response through the induction of IL-1β, IL-6, and TGF-β.