title: Eyedrop Inoculation Causes Sublethal Leptospirosis in Mice.
abstract: Leptospirosis is potentially a fatal zoonosis acquired by contact of skin and mucosal surfaces with soil and water contaminated with infected urine. We analyzed the outcome of infection of C3H/HeJ mice withLeptospira interrogansserovar Copenhageni using an enzootic mode of transmission, the conjunctival route. Infection led to weight loss andL. interrogansdissemination from blood to urine, and spirochetes were detected in blood and urine simultaneously. The infectious dose that led to consistent dissemination to kidney after conjunctival infection was ∼108leptospires. Interestingly, a lower number of spirochetes appeared to colonize the kidney, given that we quantified ∼105and ∼10 leptospires per μl of urine and per μg of kidney, respectively. Leptospira-specific IgM and IgG were detected at 15 days postinfection, and isotyping of the Ig subclass showed that the total IgG response switched from an IgG1 response to an IgG3 response after infection withL. interrogansHistological periodic acid-Schiff D staining of infected kidney showed interstitial nephritis, mononuclear cell infiltrates, and reduced size of glomeruli. Quantification of proinflammatory immunomediators in kidney showed that keratinocyte-derived chemokine, macrophage inflammatory protein 2, RANTES, tumor necrosis factor alpha, gamma interferon, and interleukin-10 were upregulated in infected mice. We show that the kinetics of disease progression after infection via the ocular conjunctiva is delayed compared with infection via the standard intraperitoneal route. Differences may be related to the number ofL. interrogansspirochetes that succeed in overcoming the natural defenses of the ocular conjunctiva and transit through tissue.
authors.affiliation: Department of Comparative Medicine, University of Tennessee Health Science Center, College of Medicine, Memphis, Tennessee, USA.
authors.forename: Joseph Pierce
authors.initials: JP
authors.lastname: Sullivan
authors.affiliation: Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee, USA.
authors.forename: Nisha
authors.initials: N
authors.lastname: Nair
authors.affiliation: Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science 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 Science Center, Memphis, Tennessee, USA mgomesso@uthsc.edu.|Immuno Technologies Inc., Memphis, Tennessee, USA.
authors.forename: Maria
authors.identifier: http://orcid.org/0000-0002-3715-4543
authors.initials: M
authors.lastname: Gomes-Solecki
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D003234:Conjunctivitis, Bacterial / Q000276:immunology / Q000382:microbiology / Q000473:pathology / Q000635:transmission; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D018836:Inflammation Mediators / Q000378:metabolism; D007921:Leptospira interrogans / Q000276:immunology; D007922:Leptospirosis / Q000276:immunology / Q000382:microbiology* / Q000401:mortality / Q000635:transmission*; D051379:Mice; D008809:Mice, Inbred C3H; D009393:Nephritis / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D009883:Ophthalmic Solutions / Q000009:adverse effects
chemical_list: D000907:Antibodies, Bacterial; D016207:Cytokines; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D018836:Inflammation Mediators; D009883:Ophthalmic Solutions
keywords: C3H/HeJ; Leptospira; conjunctiva; enzootic transmission; inflammation; mouse model; sublethal infection