Th17 Cells Mediate Clade-Specific, Serotype-Independent Mucosal Immunity

Abstract

SUMMARY The interleukin-17 (IL-17) family of cytokines phylogenetically pre-dates the evolution of T cells in jawed vertebrates, suggesting that the ontogeny of the Th17 cell lineage must have arisen to confer an evolutionary advantage to the host over innate sources of IL-17. Using a model of mucosal immunization with the encapsulated bacteria Klebsiella pneumoniae, B cells largely recognized polysaccharide capsular antigens, which limited protection to only the vaccine strain. In contrast, memory Th17 cells proliferated in response to conserved outer membrane proteins and conferred protection against several serotypes of K. pneumoniae, including the recently described multi-drug resistant New Dehli metallolactamase strain. Notably, this heterologous, clade specific protection was antibody-independent, demonstrating the Th17 cell lineage confers a host advantage by providing heterologous mucosal immunity independent of serotype specific antibody.

Helper T-Cell Type 17 Cytokines and Immunity in the Lung

“…These Th17 cells show broad specificity as they are capable of recognizing other Enterobacteriaceae family members and proliferate in a class II MHC-restricted fashion. One potential group of antigens that may explain this are outer membrane proteins (23). This broad reactivity has also been demonstrated for fungal-specific Th17 cells (31).…”

“…This early IL-17 response is dominated by gd T cells (21)(22)(23) and to a lesser extent by invariant natural killer T (iNKT) cells in the LPS model (24). It has also been shown that ozone exposure can also rapidly induce IL-17 iNKT cells in the lung (25).…”

“…In the setting of experimental K. pneumoniae infection the majority of IL-17-producing cells are gd T cells. However, after mucosal immunization with heatkilled K. pneumoniae, by 14-21 days this response is replaced by Th17 cells (23). These Th17 cells show broad specificity as they are capable of recognizing other Enterobacteriaceae family members and proliferate in a class II MHC-restricted fashion.…”

Enhanced production of IL-17A in patients with severe asthma is inhibited by 1α,25-dihydroxyvitamin D3 in a glucocorticoid-independent fashion

“…Th17 cells are critical for defence against bacterial and fungal infections (11). Mouse models demonstrate that animals deficient in IL-17A or IL-17RA are highly susceptible to infection with mucosal pathogens such as Klebsiella pneumoniae, and Candida albicans (12,13).…”

IκBNS Regulates Murine Th17 Differentiation during Gut Inflammation and Infection

“…Today, we know that Th17 cells are essential for host protection against a variety of extracellular bacteria and fungi located predominantly in the gastrointestinal tract, skin, and lungs. Consequently, most Th17 cells are found in these mucosal tissues upon infection; however, some reside in the lamina propria (LP) under steady-state conditions (4,5). Th17 cells depend on the transcription factor RORgt (6) and primarily produce the cytokine IL-17A, which is a potent inducer of other proinflammatory cytokines, such as IL-6, IL-1b, and TNF-a, in a variety of IL-17R-expressing cell types, including endothelial cells, epithelial cells, and macrophages (7,8).…”