Innate Inhibition of Adaptive Immunity: Mycobacterium tuberculosis-Induced IL-6 Inhibits Macrophage Responses to IFN-γ

Vijaya Nagabhushanam, Alejandra Solache, Li Min Ting, Claire J. Escaron, Jennifer Y. Zhang, Joel D. Ernst

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166 Scopus citations

Abstract

In humans and in mice, control of the intracellular pathogen, Mycobacterium tuberculosis (Mtb), requires IFN-γ. Although the adaptive immune response results in production of substantial amounts of IFN-γ in response to Mtb, the immune response is unable to eradicate the infection in most cases. We have previously reported evidence that Mtb inhibits macrophage responses to IFN-γ, suggesting that this may limit the ability of IFN-γ to stimulate macrophages to kill Mtb. We have also observed that uninfected macrophages, adjacent to infected macrophages in culture, exhibit decreased responses to IFN-γ. Here we report that IL-6 secreted by Mtb-infected macrophages inhibits the responses of uninfected macrophages to IFN-γ. IL-6 selectively inhibits a subset of IFN-y-responsive genes at the level of transcriptional activation without inhibiting activation or function of STAT1. Inhibition of macrophage responses to IFN-γ by IL-6 requires new protein synthesis, but this effect is not attributable to suppressor of cytokine signaling 1 or 3. These results reveal a novel function for IL-6 and indicate that IL-6 secreted by Mtb-infected macrophages may contribute to the inability of the cellular immune response to eradicate infection.

Original languageEnglish (US)
Pages (from-to)4750-4757
Number of pages8
JournalJournal of Immunology
Volume171
Issue number9
StatePublished - Oct 1 2003

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ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

Cite this

Nagabhushanam, V., Solache, A., Ting, L. M., Escaron, C. J., Zhang, J. Y., & Ernst, J. D. (2003). Innate Inhibition of Adaptive Immunity: Mycobacterium tuberculosis-Induced IL-6 Inhibits Macrophage Responses to IFN-γ. Journal of Immunology, 171(9), 4750-4757.