Innate immune activation of CD4 T cells in salmonella-infected mice is dependent on IL-18.
Production of IFN-gamma by CD4 T cells is generally thought to be mediated by TCR triggering, however, Ag-nonspecific activation of effector CD8 T cells has been reported in infection models. In this study, we demonstrate that Ag-experienced CD4 T cells in the spleen of Salmonella-infected mice acquire the capacity to rapidly secrete IFN-gamma in response to stimulation with bacterial lysate or LPS. This innate responsiveness of T cells was transient and most apparent during, and immediately following, active Salmonella infection. Furthermore, innate T cell production of IFN-gamma in response to bacterial lysate or LPS was Ag independent and could be induced in Listeria-infected mice and in the absence of MHC class II expression. IL-18 was required for maximal innate responsiveness of CD4 T cells in Salmonella-infected mice and for optimal bacterial clearance in vivo. These data demonstrate that CD4 T cells acquire the capacity to respond to innate stimuli during active bacterial infection, a process that may contribute significantly to amplifying effector responses in vivo.
Srinivasan
Aparna
A
Department of Medicine, and Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota Medical School, McGuire Translational Research Facility, Minneapolis, MN 55455, USA.
Salazar-Gonzalez
Rosa-Maria
RM
Jarcho
Michael
M
Sandau
Michelle M
MM
Lefrancois
Leo
L
McSorley
Stephen J
SJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D002469:Cell Separation; D007113:Immunity, Innate / Q000235:genetics; D007371:Interferon-gamma / Q000378:metabolism; D020382:Interleukin-18 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D008089:Listeria monocytogenes / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D012481:Salmonella Infections, Animal / Q000235:genetics / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology
D020382:Interleukin-18; D007371:Interferon-gamma