title: Mouse model for sublethal Leptospira interrogans infection.
abstract: Although Leptospira can infect a wide range of mammalian species, most studies have been conducted in golden Syrian hamsters, a species particularly sensitive to acute disease. Chronic disease has been well characterized in the rat, one of the natural reservoir hosts. Studies in another asymptomatic reservoir host, the mouse, have occasionally been done and have limited infection to mice younger than 6 weeks of age. We analyzed the outcome of sublethal infection of C3H/HeJ mice older than age 10 weeks with Leptospira interrogans serovar Copenhageni. Infection led to bloodstream dissemination of Leptospira, which was followed by urinary shedding, body weight loss, hypothermia, and colonization of the kidney by live spirochetes 2 weeks after infection. In addition, Leptospira dissemination triggered inflammation in the kidney but not in the liver or lung, as determined by increased levels of mRNA transcripts for the keratinocyte-derived chemokine, RANTES, macrophage inflammatory protein 2, tumor necrosis factor alpha, interleukin-1β, inducible nitric oxide synthase, interleukin-6, and gamma interferon in kidney tissue. The acquired humoral response to Leptospira infection led to the production of IgG mainly of the IgG1 subtype. Flow cytometric analysis of splenocytes from infected mice revealed that cellular expansion was primarily due to an increase in the levels of CD4(+) and double-negative T cells (not CD8(+) cells) and that CD4(+) T cells acquired a CD44(high) CD62L(low) effector phenotype not accompanied by increases in memory T cells. A mouse model for sublethal Leptospira infection allows understanding of the bacterial and host factors that lead to immune evasion, which can result in acute or chronic disease or resistance to infection (protection).
authors.affiliation: Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA Immuno Technologies Inc., Memphis, Tennessee, USA.
authors.forename: Luciana
authors.initials: L
authors.lastname: Richer
authors.affiliation: Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA Immuno Technologies Inc., Memphis, Tennessee, USA.
authors.forename: Hari-Hara
authors.initials: HH
authors.lastname: Potula
authors.affiliation: Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA.
authors.forename: Rita
authors.initials: R
authors.lastname: Melo
authors.affiliation: Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA.
authors.forename: Ana
authors.initials: A
authors.lastname: Vieira
authors.affiliation: Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Sciences Center, Memphis, Tennessee, USA Immuno Technologies Inc., Memphis, Tennessee, USA mgomesso@uthsc.edu.
authors.forename: Maria
authors.initials: M
authors.lastname: Gomes-Solecki
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D001437:Bacteriuria / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes; D018946:Chemokine CCL5 / Q000235:genetics / Q000276:immunology; D054426:Chemokine CXCL2 / Q000235:genetics / Q000276:immunology; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D007035:Hypothermia / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology; D053583:Interleukin-1beta / Q000235:genetics / Q000276:immunology; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology; D007668:Kidney / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D007921:Leptospira interrogans / Q000276:immunology*; D007922:Leptospirosis / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D051379:Mice / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D008809:Mice, Inbred C3H; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology; D015431:Weight Loss / Q000276:immunology
chemical_list: C503460:Ccl5 protein, mouse; D018946:Chemokine CCL5; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse; D007074:Immunoglobulin G; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C074302:keratinocyte-derived chemokines; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse