Interleukin‐6 regulates the phenotype of the immune response to a tuberculosis subunit vaccine

Abstract

Summary We investigated the role of interleukin‐6 (IL‐6) in the development of the immune response to a subunit vaccine against tuberculosis consisting of the culture filtrate proteins of Mycobacterium tuberculosis emulsified in the adjuvant dimethyldioctadecylammonium bromide (DDA). C57Bl/6 mice immunized with this vaccine developed a strong T helper 1 (Th1) response characterized by an increased production of interferon‐γ (IFN‐γ) secreted by CD4+ T cells. Neutralization of IL‐6 during in vivo priming resulted in marked reduction in the ability of T cells to secrete IFN‐γ and IL‐2 and to proliferate. IL‐6 gene‐disrupted mice primed with the vaccine showed a decrease in the number of IFN‐γ‐producing cells and an increase in IL‐4‐secreting cells as compared to control mice. In contrast, neutralization of IL‐6 during a boost of the vaccine in previously primed mice did not affect the development of IFN‐γ‐producing cells but still increased the number of IL‐4‐producing cells. Our work shows that IL‐6 plays a major role in the priming but not in the later expression of a Th1 response to a tuberculosis vaccine.

NK Cells Influence Both Innate and Adaptive Immune Responses after Mucosal Immunization with Antigen and Mucosal Adjuvant

“…Previous studies have shown that NK cells enhance IL-6 production, by MFs and DCs, during early immune responses (45,46). Other studies concentrating on M. tuberculosis have shown that IL-6 is required for early IFN-g production in the lungs of mice infected with M. tuberculosis, and that IL-6 participates in the induction of protective T H 1 T cell responses during vaccination (47)(48)(49). Interestingly, several recent studies have focused on the role of NK cells in IL-22 production (37).…”

Intragranulomatous necrosis in lungs of mice infected by aerosol with Mycobacterium tuberculosis is related to bacterial load rather than to any one cytokine or T cell type

“…Finally, the lack of IL-6 neither affected the induction of INPG nor triggered a massive pattern. This cytokine is associated with stimulation of Th1 immunity at the beginning of infection, but does not affect the bacillary load as much as other Th1-related cytokines [42]. Interestingly, the presence or absence of CD8 þ cells, which may contribute to cytotoxicity in M. tuberculosis infection and thus be a key cell population in the induction of necrosis [20], was not significant either for the development of INPG.…”

The two faces of IL-6 in the tumor microenvironment

“…In this regard, IL-6, which is largely produced by DC in the lymph node has been demonstrated to impact the activation, expansion, survival, and polarization of T cells during an immune response [70]. In various immunization settings, IL-6 signaling is required for optimal T cell priming, the induction of a productive IFN-γ response, protection of T cells from the suppressive activities of Treg, and the acquisition of the ability to provide help to B cells [71–73]. In addition to driving the development of CD8 + lymphocyte effector functions, IL-6 has also been described as promoting T cell proliferation following T cell receptor stimulation [5,52].…”