Expression of Toll/IL-1R domain-containing adaptor protein (TIRAP) is detrimental to primary clearance of Salmonella and is not required for the generation of protective immunity.
Salmonella infection triggers activation of innate immune cells through the interaction of bacterial products with Toll-like receptors (TLRs). Toll/IL-1R domain-containing adaptor protein (TIRAP) is an adaptor protein involved in downstream signaling through TLRs 1, 2, 4, and 6. We examined the role of TIRAP during infection with attenuated Salmonella. Surprisingly, TIRAP-deficient mice were fully capable of resolving primary infection with Salmonella and actually exhibited accelerated clearance of bacteria at a late stage of the infection. Consistent with enhanced bacterial clearance, TIRAP-deficient mice resolved bacterial-associated splenic inflammation more rapidly than wild-type (Wt) mice and splenocytes from Salmonella-infected TIRAP-deficient mice produced more IFN-gamma upon in vitro re-stimulation. Upon secondary challenge, TIRAP-deficient and Wt mice displayed a similar level of protective immunity against virulent Salmonella. Together these data indicate that TIRAP-mediated signaling is completely dispensable for clearance of Salmonella infection, and actually has a mild deleterious effect upon the resolution of primary infection.
Jerke
Stu
S
Center for Infectious Diseases and Microbiology Translational Research, University of Minnesota Medical School, Minneapolis, MN 55455, United States.
Srinivasan
Aparna
A
McSorley
Stephen J
SJ
D019264:Adoptive Transfer; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D000942:Antigens, Bacterial / Q000276:immunology; D015169:Colony Count, Microbial; D000939:Epitopes; D054884:Host-Pathogen Interactions; D007110:Immunity, Active / Q000235:genetics*; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D046709:Pattern Recognition, Physiological; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000276:immunology*; D012480:Salmonella Infections / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012486:Salmonella typhimurium; D015398:Signal Transduction; D013154:Spleen / Q000276:immunology / Q000382:microbiology; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D000939:Epitopes; D008562:Membrane Glycoproteins; D017472:Receptors, Interleukin-1; C434984:TIRAP protein, human; D007371:Interferon-gamma