Toll-like Receptor and Inflammasome Signals Converge to Amplify the Innate Bactericidal Capacity of T Helper 1 Cells

Hope O'Donnell, Oanh H. Pham, Lin xi Li, Shaikh M. Atif, Seung Joo Lee, Marietta M. Ravesloot, Jessica L. Stolfi, Sean Paul Nuccio, Petr Broz, Denise M. Monack, Andreas J Baumler, Stephen J Mcsorley

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

T cell effector functions can be elicited by noncognate stimuli, but the mechanism and contribution of this pathway to the resolution of intracellular macrophage infections have not been defined. Here, we show that CD4+ T helper 1 (Th1) cells could be rapidly stimulated by microbe-associated molecular patterns during active infection with Salmonella or Chlamydia. Further, maximal stimulation of Th1 cells by lipopolysaccharide (LPS) did not require T-cell-intrinsic expression of toll-like receptor 4 (TLR4), interleukin-1 receptor (IL-1R), or interferon-γ receptor (IFN-γR) but instead required IL-18R, IL-33R, and adaptor protein MyD88. Innate stimulation of Th1 cells also required host expression of TLR4 and inflammasome components that together increased serum concentrations of IL-18. Finally, the elimination of noncognate Th1 cell stimulation hindered the resolution of primary Salmonella infection. Thus, the invivo bactericidal capacity of Th1 cells is regulated by the response to noncognate stimuli elicited by multiple innate immune receptors.

Original languageEnglish (US)
Pages (from-to)213-224
Number of pages12
JournalImmunity
Volume40
Issue number2
DOIs
StatePublished - Feb 20 2014

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases
  • Immunology

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    O'Donnell, H., Pham, O. H., Li, L. X., Atif, S. M., Lee, S. J., Ravesloot, M. M., Stolfi, J. L., Nuccio, S. P., Broz, P., Monack, D. M., Baumler, A. J., & Mcsorley, S. J. (2014). Toll-like Receptor and Inflammasome Signals Converge to Amplify the Innate Bactericidal Capacity of T Helper 1 Cells. Immunity, 40(2), 213-224. https://doi.org/10.1016/j.immuni.2013.12.013