Recognition of Toxoplasma gondii by TLR11 prevents parasite-induced immunopathology.
TLRs are thought to play a critical role in self/non-self discrimination by sensing microbial infections and initiating both innate and adaptive immunity. In this study, we demonstrate that in the absence of TLR11, a major TLR involved in recognition of Toxoplasma gondii, infection with this protozoan parasite induces an abnormal immunopathological response consisting of pancreatic tissue destruction, fat necrosis, and systemic elevations in inflammatory reactants. We further show that this immunopathology is the result of non-TLR dependent activation of IFN-gamma secretion by NK cells in response to the infection. These findings reveal that in addition to triggering host resistance to infection, TLR recognition can be critical for the prevention of pathogen-induced immune destruction of self tissue.
Yarovinsky
Felix
F
Department of Immunology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA. Felix.Yarovinsky@UTSouthwestern.edu
Hieny
Sara
S
Sher
Alan
A
D000208:Acute Disease; D000818:Animals; D005218:Fat Necrosis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D007371:Interferon-gamma / Q000378:metabolism; D007694:Killer Cells, Natural / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D010195:Pancreatitis / Q000235:genetics / Q000276:immunology / Q000473:pathology; D051193:Toll-Like Receptors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D014122:Toxoplasma / Q000276:immunology* / Q000378:metabolism; D014123:Toxoplasmosis / Q000235:genetics / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control*
C482903:Tlr11 protein, mouse; D051193:Toll-Like Receptors; D007371:Interferon-gamma