The crucial roles of Th17-related cytokines/signal pathways in M. tuberculosis infection

Abstract

Interleukin-17 (IL-17), IL-21, IL-22 and IL-23 can be grouped as T helper 17 (Th17)-related cytokines because they are either produced by Th17/Th22 cells or involved in their development. Here, we review Th17-related cytokines/Th17-like cells, networks/signals and their roles in immune responses or immunity against Mycobacterium tuberculosis (Mtb) infection. Published studies suggest that Th17-related cytokine pathways may be manipulated by Mtb microorganisms for their survival benefits in primary tuberculosis (TB). In addition, there is evidence that immune responses of the signal transducer and activator of transcription 3 (STAT3) signal pathway and Th17-like T-cell subsets are dysregulated or destroyed in patients with TB. Furthermore, Mtb infection can impact upstream cytokines in the STAT3 pathway of Th17-like responses. Based on these findings, we discuss the need for future studies and the rationale for targeting Th17-related cytokines/signals as a potential adjunctive treatment.

Cell-Mediated Immune Responses to in vivo-Expressed and Stage-Specific Mycobacterium tuberculosis Antigens in Latent and Active Tuberculosis Across Different Age Groups

“…As for IFN-γ, there is no unequivocal evidence defining IL-17A, GM-CSF, and IP-10 as essential to controlling latent Mtb infection (43)(44)(45)(46)(47) or active TB disease (48)(49)(50)(51). TNF-α, generally associated with tissue damage (42,52), is also considered a key factor in TB granuloma integrity and protective immunity (53).…”

T lymphocytes in the intestinal mucosa: defense and tolerance

“…Intestinal T cells protect the host from bacterial invasion either by direct killing or the production of numerous cytokines. 52 Enteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli Citrobacter rodentium (C. rod), which infects mice and shares several pathogenic mechanisms with EPEC and EHEC, has become the principal rodent model in studies investigating infections by those enteropathogens. In cases of extracellular C. rod infection, the cytokines secreted by Th17 cells, such as IL17A, IL17F, and IL22, exert protective effects.…”

Innate lymphoid cells in lung infection and immunity

“…On the contrary, using a mouse model of BCG‐immunized mice, no functional differences in the capacity of splenic‐derived NK cells to produce IFN‐γ could be detected in a secondary in vitro exposure to BCG . Several published studies point out that Th17‐associated cytokines might influence the course of M. tuberculosis infection but the definite role of IL‐17 during primary TB is uncertain . One report stated that innate‐like CD3 − CD4 − CD8 − γδTCR − Thy1.2 + cells are a major source of IFN‐γ, but also IL‐17A, in the lungs during challenge with M. tuberculosis in BCG‐vaccinated mice .…”