Il-10 deficient mice express IFN-γ mRNA and clear Leptospira interrogans from their kidneys more rapidly than normal C57BL/6 mice |
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| Institution: | 1. Reynolds American, Inc. 401 N. Main St., Winston Salem, NC 27101, United States;2. Immunity, Inflammation and Disease Laboratory, Division of Intramural Research, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC, United States;3. Galaxy Diagnostics, Inc. 7020 Kit Creek Rd., Ste 130, Research Triangle Park, NC 27709, United States;4. Department of Biological Sciences, North Carolina State University, Raleigh, NC 27695, United States;1. Key Laboratory of Tropical Marine Bio-resources and Ecology and Guangdong Provincial Key Laboratory of Applied Marine Biology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, Guangzhou 510301, China;2. South China Sea Bio-Resource Exploitation and Utilization Collaborative Innovation Center, Guangzhou 510275, China;3. Department of Biological and Environmental Engineering, Changsha University, Changsha 410022, China;1. Immune Recovery Section, Department of Internal Medicine II, Division of Hematology, University Hospital of Würzburg, Würzburg, Germany;2. Institute of Virology, University of Würzburg, Würzburg, Germany;1. Institution of Pathogenic Biology, Medical College, University of South China; Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China; Hunan Provincial Key Laboratory for Special Pathogens Prevention and Control, University of South China, Hengyang 421001, China;2. Department of Clinical Laboratory, The Second Affiliated Hospital of University of South China, Hengyang 421001, China;3. Department of Laboratory Medicine, The Second Xiangya Hospital, Central South University, Changsha 410011, China;1. Department of Infectious Diseases, Medical Microbiology and Hygiene, University Hospital Heidelberg, 69120 Heidelberg, Germany;2. International Centre for Genetic Engineering and Biotechnology (ICGEB) & Institute of Infectious Disease and Molecular Medicine (IDM), Division of Immunology, University of Cape Town & South African Medical Research Council (SAMRC), South Africa;3. Translational Lung Research Center Heidelberg (TLRC), Member of the German Center for Lung Research (DZL);1. Key Laboratory for Oral Biomedical Research of Shandong Province, School of Dentistry, Shandong University, Jinan, China;2. Yuhuangding Hospital, Yantai, China |
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| 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 16 s mRNA was detected in both lung and kidney tissues within a day after infection. Levels of 16 s mRNA then dropped in both organs with complete elimination from the lung by day 3 but persistence in the kidney for 7 days 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. |
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| Keywords: | Leptospirosis Innate immunity IL-10 |
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