The adaptor molecule Trif contributes to murine host defense during Leptospiral infection.
Leptospirosis is a zoonotic disease and is caused by pathogenic species of the Leptospira genus, including Leptospira interrogans (L. interrogans). Humans, domestic and wild animals are susceptible to acute or chronic infection. The innate immune response is a critical defense mechanism against Leptospira interrogans, and has been investigated in mouse models. Murine Toll-like receptors (TLRs) have been shown to be key factors in sensing and responding to L. interrogans infection. Specifically, TLR2, TLR4 and the TLR adaptor molecule MyD88 are essential for host defense against L. interrogans; however, the role of the TLR adaptor molecule TIR-domain-containing adaptor-inducing interferon β (TRIF) in the response to L. interrogans has not been previously determined. In the present study, TRIF was found to play an important role during leptospiral infection. Following challenge with L. interrogans, Trif(-/-) mice exhibited delayed weight gain compared to wild-type mice. Moreover, Trif(-/-) mice exhibited an increase in L. interrogans burden in the kidneys, lungs, and blood at early time points (less than 7days post infection). Multiple components of the innate immune responses were dampened in response to leptospiral infection including transcription and production of cytokines, and the humoral response, which suggested that TRIF contributes to expression and production of cytokines important for the host defense against L. interrogans.
Department of Biological Sciences, North Carolina State University, Raleigh, NC, United States.
Priya A
PA
Jayaraman
Department of Biological Sciences, North Carolina State University, Raleigh, NC, United States.
Amy A
AA
Devlin
Department of Biological Sciences, North Carolina State University, Raleigh, NC, United States.
Jennifer C
JC
Miller
Department of Biological Sciences, North Carolina State University, Raleigh, NC, United States. Electronic address: fscholl@ncsu.edu.
Frank
F
Scholle
D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000276:immunology*; D000818:Animals; D016207:Cytokines / Q000097:blood / Q000235:genetics / Q000276:immunology; D007070:Immunoglobulin A / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D007668:Kidney / Q000276:immunology; D007919:Leptospira / Q000276:immunology; D007922:Leptospirosis / Q000276:immunology*; D008168:Lung / Q000276:immunology; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger / Q000378:metabolism
D033942:Adaptor Proteins, Vesicular Transport; D016207:Cytokines; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D012333:RNA, Messenger; C476286:Ticam1 protein, mouse
Innate immunity; Leptospira interrogans; Leptospirosis; TRIF