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We analyzed the outcome of infection of C3H\/HeJ mice with<jats:named-content content-type=\"genus-species\">Leptospira interrogans<\/jats:named-content>serovar Copenhageni using an enzootic mode of transmission, the conjunctival route. Infection led to weight loss and<jats:named-content content-type=\"genus-species\">L. interrogans<\/jats:named-content>dissemination 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 \u223c10<jats:sup>8<\/jats:sup>leptospires. Interestingly, a lower number of spirochetes appeared to colonize the kidney, given that we quantified \u223c10<jats:sup>5<\/jats:sup>and \u223c10 leptospires per \u03bcl of urine and per \u03bcg 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 with<jats:named-content content-type=\"genus-species\">L. interrogans<\/jats:named-content>. Histological 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 of<jats:named-content content-type=\"genus-species\">L. interrogans<\/jats:named-content>spirochetes that succeed in overcoming the natural defenses of the ocular conjunctiva and transit through tissue.<\/jats:p>","DOI":"10.1128\/iai.01050-16","type":"journal-article","created":{"date-parts":[[2017,1,24]],"date-time":"2017-01-24T02:30:21Z","timestamp":1485225021000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":22,"title":["Eyedrop Inoculation Causes Sublethal Leptospirosis in Mice"],"prefix":"10.1128","volume":"85","author":[{"given":"Joseph Pierce","family":"Sullivan","sequence":"first","affiliation":[{"name":"Department of Comparative Medicine, University of Tennessee Health Science Center, College of Medicine, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nisha","family":"Nair","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hari-Hara","family":"Potula","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee, USA"},{"name":"Immuno Technologies Inc., Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3715-4543","authenticated-orcid":false,"given":"Maria","family":"Gomes-Solecki","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, Memphis, Tennessee, USA"},{"name":"Immuno Technologies Inc., Memphis, Tennessee, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0003898"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(03)00830-2"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2010.06.012"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-662-45059-8_5"},{"key":"e_1_3_3_6_2","first-page":"85","article-title":"Leptospirosis in the city of Salvador, Bahia, Brazil: a case-control seroepidemiologic study","volume":"6","author":"Caldas EM","year":"1979","unstructured":"Caldas EM Sampaio MB . 1979. 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