The route of infection with Leptospira interrogans serovar Copenhageni affects the kinetics of bacterial dissemination and kidney colonization
| Autor: | Nisha Nair, Maria Gomes-Solecki, Catherine Werts, Mariana Soares Guedes |
|---|---|
| Přispěvatelé: | 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), Institut Pasteur [Paris] |
| Rok vydání: | 2020 |
| Předmět: |
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 |
| Zdroj: | PLoS Neglected Tropical Diseases PLoS Neglected Tropical Diseases, 2020, 14 (1), pp.e0007950. ⟨10.1371/journal.pntd.0007950⟩ PLoS Neglected Tropical Diseases, Public Library of Science, 2020, 14 (1), pp.e0007950. ⟨10.1371/journal.pntd.0007950⟩ PLoS Neglected Tropical Diseases, Vol 14, Iss 1, p e0007950 (2020) |
| ISSN: | 1935-2735 1935-2727 |
| DOI: | 10.1371/journal.pntd.0007950 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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