1. The route of infection with Leptospira interrogans serovar Copenhageni affects the kinetics of bacterial dissemination and kidney colonization
- Author
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Nisha Nair, Maria Gomes-Solecki, Catherine Werts, Mariana Soares Guedes, The University of Tennessee Health Science Center [Memphis] (UTHSC), Immuno Technologies Inc [Memphis], Biologie et Génétique de la Paroi bactérienne - Biology and Genetics of Bacterial Cell Wall (BGPB), Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris]
- Subjects
Bacterial Diseases ,MESH: Mouth Mucosa ,0301 basic medicine ,MESH: Leptospira interrogans ,MESH: Immunoglobulins ,Physiology ,RC955-962 ,Respiratory System ,Mucous membrane of nose ,Urine ,Pathology and Laboratory Medicine ,[SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity ,MESH: Urine ,0302 clinical medicine ,Arctic medicine. Tropical medicine ,Zoonoses ,Medicine and Health Sciences ,MESH: Animals ,Oral mucosa ,Skin ,Leptospira ,Mice, Inbred C3H ,Kidney ,Nephritis ,MESH: Kinetics ,biology ,Animal Models ,MESH: Leptospirosis ,Leptospirosis ,Bacterial Pathogens ,Body Fluids ,3. Good health ,Leptospira Interrogans ,Blood ,Infectious Diseases ,medicine.anatomical_structure ,Experimental Organism Systems ,Medical Microbiology ,MESH: Nasal Mucosa ,MESH: Immunity, Innate ,Public aspects of medicine ,RA1-1270 ,Pathogens ,Anatomy ,MESH: Nephritis ,Leptospira interrogans ,Research Article ,Neglected Tropical Diseases ,030231 tropical medicine ,Immunoglobulins ,Mouse Models ,Research and Analysis Methods ,Microbiology ,03 medical and health sciences ,Model Organisms ,MESH: Skin ,Immunity ,medicine ,Animals ,MESH: Mice, Inbred C3H ,Microbial Pathogens ,[SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health ,Innate immune system ,Bacteria ,business.industry ,Mouth Mucosa ,Organisms ,Public Health, Environmental and Occupational Health ,Biology and Life Sciences ,Kidneys ,Renal System ,Tropical Diseases ,biology.organism_classification ,medicine.disease ,[SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology ,Immunity, Innate ,Kinetics ,Nasal Mucosa ,030104 developmental biology ,Animal Studies ,business - Abstract
The goal of this study was to characterize how natural routes of infection affect the kinetics of pathogenic Leptospira dissemination to blood and kidney. C3H/HeJ mice were sublethally infected with L. interrogans serovar Copenhageni FioCruz L1-130 (Leptospira) through exposure of a dermis wound and through oral and nasal mucosa, in comparison to uninfected mice and to mice infected via standard intraperitoneal inoculation. In striking contrast to oral mucosa inoculation, transdermal and nasal mucosa infections led to weight loss, renal colonization and inflammation, as previously observed for conjunctival and intraperitoneal infections. However, the timing at which Leptospira gained access to blood, as well as Leptospira’ colonization of the kidney and shedding in urine, differed from intraperitoneal infection. Furthermore, a comparative analysis of transcription of pro-inflammatory mediators in kidney and total immunoglobulin isotyping in serum from infected mice, showed increased innate immune response markers (KC, MIP-2, TNF-α) and lower Th1 associated IFN-γ in kidney, as well as lower Th1 associated IgG2a in mice infected through the nasal mucosa as compared to intraperitoneal infection. We conclude that the route of infection affects the timing at which Leptospira gains access to blood for dissemination, as well as the dynamics of colonization and inflammation of the kidney., Author summary Leptospirosis is a neglected disease caused by pathogenic Leptospira that affects humans and animals. Hosts contract Leptospira after exposure to contaminated water through cuts and bruises on skin and mucous membranes. We hypothesized that the route of infection may affect the kinetics of Leptospira dissemination to tissues and leptospirosis progression. In this study, we evaluated the clinical outcomes, and kidney colonization and inflammation after exposure of mice to pathogenic Leptospira using three natural routes of infection. In contrast to transdermal and nasal mucosa, infection through oral mucosa did not cause weight loss and did not result in renal colonization or inflammation. We also found that different natural routes of infection affect the timing at which Leptospira gain access to blood for dissemination, as well as bacterial burden and levels of pro-inflammatory markers in kidney. Precise timing of bacterial dissemination in blood and urine are important differences to consider for assessment of clinical signs of leptospirosis and for development of diagnostic assays for direct detection of Leptospira in human and veterinary biological samples. These studies also provide disease model tools in which to test the efficacy of vaccine candidates using natural routes of infection.
- Published
- 2020