IL-23 and IL-17 in the establishment of protective pulmonary CD4+ T cell responses after vaccination and during Mycobacterium tuberculosis challenge

Abstract

Interferon-gamma is key in limiting Mycobacterium tuberculosis infection. Here we show that vaccination triggered an accelerated interferon-gamma response by CD4(+) T cells in the lung during subsequent M. tuberculosis infection. Interleukin 23 (IL-23) was essential for the accelerated response, for early cessation of bacterial growth and for establishment of an IL-17-producing CD4(+) T cell population in the lung. The recall response of the IL-17-producing CD4(+) T cell population occurred concurrently with expression of the chemokines CXCL9, CXCL10 and CXCL11. Depletion of IL-17 during challenge reduced the chemokine expression and accumulation of CD4(+) T cells producing interferon-gamma in the lung. We propose that vaccination induces IL-17-producing CD4(+) T cells that populate the lung and, after challenge, trigger the production of chemokines that recruit CD4(+) T cells producing interferon-gamma, which ultimately restrict bacterial growth.

Effects of dietary protein levels on the disease resistance, immune function and physical barrier function in the gill of grass carp ( Ctenopharyngodon idella ) after challenged with Flavobacterium columnare

“…As reported, the inhibition of proinflammatory cytokine IL-12 production increases ZO-2 expression [97], and IL-12p35 is one of the subunits of IL-12 [98] in mice. In our studies, at the optimal level of dietary protein, IL-12p35 gene expression was down-regulated, but for the mRNA level of ZO-2, there was no significant change in the intestine.…”

Protective anti‐mycobacterial T cell responses through exquisite in vivo activation of vaccine‐targeted dendritic cells

“…IL-12p70 is a central cytokine for the induction of Th1 responses and IC31 is a potent inducer of IFN-c-secreting T cells, making the IL-12p40/IL-12p35 heterodimer a likely product of IC31-activated DC. However, IL-23 (the IL-12p40 and p19 dimer), which supports IL-17-producing T cells, also contributes to IFN-c-producing T cells during vaccination and control of infection with M. tuberculosis [27]. Due to the very small number of vaccine-associated DC, detailed cytokine production patterns could not be characterized within the frame of this pilot study.…”

The use of Mycobacterium tuberculosis HspX and GlcB proteins to identify latent tuberculosis in rheumatoid arthritis patients

“…In an elegant study, Torrado and Cooper (2010) proposed that the Th17 cell population driven by the innate immune response is the first Th phenotype in TB granulomas. Thus, our results prompted us to hypothesise that Th17 cells would be a better surrogate marker for active TB once active TB patients showed specific Th17 induction ( Khader et al 2007 ). We also investigated whether there were differences in IL-6 levels between RA patients that correlated with their TB latency status.…”