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Immunity. 2014 Feb 20;40(2):213-24. doi: 10.1016/j.immuni.2013.12.013. Epub 2014 Feb 6.

Toll-like receptor and inflammasome signals converge to amplify the innate bactericidal capacity of T helper 1 cells.

Author information

1
Center for Comparative Medicine, Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA; Microbiology, Immunology, and Cancer Biology Graduate Program, University of Minnesota Medical School - Twin Cities, Minneapolis, MN 55455, USA.
2
Center for Comparative Medicine, Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA.
3
Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, CA 95616, USA.
4
Department of Microbiology and Immunology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
5
Center for Comparative Medicine, Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA. Electronic address: sjmcsorley@ucdavis.edu.

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 in vivo bactericidal capacity of Th1 cells is regulated by the response to noncognate stimuli elicited by multiple innate immune receptors.

PMID:
24508233
PMCID:
PMC3960852
DOI:
10.1016/j.immuni.2013.12.013
[Indexed for MEDLINE]
Free PMC Article

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