title: Toll-like receptor and inflammasome signals converge to amplify the innate bactericidal capacity of T helper 1 cells.
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.
authors: 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.
authors: Hope
authors: H
authors: O'Donnell
authors: Center for Comparative Medicine, Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA.
authors: Oanh H
authors: OH
authors: Pham
authors: Center for Comparative Medicine, Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA.
authors: Lin-xi
authors: LX
authors: Li
authors: Center for Comparative Medicine, Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA.
authors: Shaikh M
authors: SM
authors: Atif
authors: Center for Comparative Medicine, Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA.
authors: Seung-Joo
authors: SJ
authors: Lee
authors: Center for Comparative Medicine, Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA.
authors: Marietta M
authors: MM
authors: Ravesloot
authors: Center for Comparative Medicine, Department of Anatomy, Physiology, and Cell Biology, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616, USA.
authors: Jessica L
authors: JL
authors: Stolfi
authors: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, CA 95616, USA.
authors: Sean-Paul
authors: SP
authors: Nuccio
authors: Department of Microbiology and Immunology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
authors: Petr
authors: P
authors: Broz
authors: Department of Microbiology and Immunology, School of Medicine, Stanford University, Stanford, CA 94305, USA.
authors: Denise M
authors: DM
authors: Monack
authors: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, CA 95616, USA.
authors: Andreas J
authors: AJ
authors: Baumler
authors: 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.
authors: Stephen J
authors: SJ
authors: McSorley
mesh_terms: D000818:Animals; D058491:Bacterial Load / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology; D002689:Chlamydia / Q000502:physiology; D005434:Flow Cytometry; D007113:Immunity, Innate / Q000276:immunology*; D058847:Inflammasomes / Q000378:metabolism*; D020382:Interleukin-18 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D060888:Real-Time Polymerase Chain Reaction; D012475:Salmonella / Q000502:physiology; D015398:Signal Transduction; D018417:Th1 Cells / Q000276:immunology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051193:Toll-Like Receptors / Q000378:metabolism*
chemical_list: D015704:CD4 Antigens; D058847:Inflammasomes; D020382:Interleukin-18; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors