title: Il-10 deficient mice express IFN-γ mRNA and clear Leptospira interrogans from their kidneys more rapidly than normal C57BL/6 mice.
abstract: Leptospira interrogans (L. interrogans), the causative agent of leptospirosis, is a widespread zoonotic spirochete that lives a dual lifestyle. L. interrogans infects mice, rats, and wildlife in a persistent and asymptomatic fashion, while also causing productive and acute infections in other mammals such as humans and hamsters. Infections in humans can be fatal, accompanied by a cytokine storm and shock-like symptoms. Production of IL-10 has been noted in both rodent and human infections which has led a number of investigators to hypothesize that IL-10 plays a role in the pathogenesis of this disease. To test this hypothesis we have compared bacteremia and the cytokine response of normal and IL-10 deficient C57Bl/6 mice following ip infection with L. interrogans. In normal mice bacterial 16s mRNA was detected in both lung and kidney tissues within a day after infection. Levels of 16s mRNA then dropped in both organs with complete elimination from the lung by day 3 but persistence in the kidney for 7days after infection. In contrast, in IL-10 deficient mice, the organism was eliminated more rapidly from the kidney. We found that infection of both control and IL-10 deficient mice produced similar levels of a number of pro-inflammatory cytokine mRNAs. On the other hand, IFN-γ mRNA was only induced in IL-10 deficient mice. These results support the hypothesis that L. interrogans ability to induce IL-10, which in turn prevents production of IFN-γ and inhibits T cell immunity, may contribute to the persistent growth of this microorganism in the murine kidney.
authors.affiliation: Reynolds American, Inc. 401 N. Main St., Winston Salem, NC 27101, United States.
authors.forename: Amy A
authors.initials: AA
authors.lastname: Devlin
authors.affiliation: Immunity, Inflammation and Disease Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, United States.
authors.forename: Priya J
authors.initials: PJ
authors.lastname: Halvorsen
authors.affiliation: Galaxy Diagnostics, Inc. 7020 Kit Creek Rd., Ste 130, Research Triangle Park, NC 27709, United States.
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Miller
authors.affiliation: Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695, United States. Electronic address: smlaster@ncsu.edu.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Laster
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D007075:Immunoglobulin M / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics*; D016753:Interleukin-10 / Q000172:deficiency*; D007668:Kidney / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D007921:Leptospira interrogans / Q000276:immunology*; D007922:Leptospirosis / Q000235:genetics* / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012333:RNA, Messenger
chemical_list: D000907:Antibodies, Bacterial; D016207:Cytokines; D007075:Immunoglobulin M; D012333:RNA, Messenger; D016753:Interleukin-10; D007371:Interferon-gamma
keywords: IL-10; Innate immunity; Leptospira interrogans; Leptospirosis