Th17 cells at the crossroads of innate and adaptive immunity against infectious diseases at the mucosa

Abstract

T helper type 17 (Th17) cells are a distinct lineage of T cells that produce the effector molecules IL-17, IL-17F, IL-21, and IL-22. Although the role of Th17 cells in autoimmunity is well documented, there is growing evidence that the Th17 lineage and other interleukin (IL)-17-producing cells are critical for host defense against bacterial, fungal, and viral infections at mucosal surfaces. Here we summarize recent progress in our understanding of the function of IL-17-producing cells as a bridge between innate and adaptive immunity against infectious diseases at the mucosa.

Figure 1. Current understanding of T-helper cell differentiation

Naïve CD4+ T cells, after activation by signaling via the T-cell Receptor and co-stimulatory molecules such as CD28 and Cytotoxic T lymphocyte-associated protein 4 (CTLA-4), can differentiate into three lineages of effector T helper(Th) cells namely Th1, Th2 or Th17 cells. Th subsets produce different cytokines and have distinct immunoregulatory functions. Th2 cells produce IL-4, IL-5 and IL-10 and promote immunity against parasites such as helminths. Th1 cells produce IFNγ and TNF-α and provide immunity against intracellular pathogens. Th17 cells produce the cytokines IL-17/IL-17F, IL-22, IL-21 and TNF-α and primarily promote immunity against extracellular pathogens.

Figure 2. Role of Th17 cytokines in protective immunity at the mucosa

Infection-induced IL-17 and IL-22 can be produced by several immune cells found in mucosal sites. A critical likely target of IL-17 and IL-22 is the mucosal epithelium where IL-17 augments G-CSF and CXC chemokine production resulting in recruitment of neutrophils that contribute to bacterial and fungal clearance at mucosal sites. IL-22 along with IL-17 also augments antimicrobial peptides and epithelial repair function important for control of extracellular fungal pathogens. In the setting of vaccine-induced immunity, Th17 cells can induce the production of ligands for CXCR3 and augment the recruitment of IFNγ producing Th1 cells to control intracellular pathogen growth.