Submitted to: Infection and Immunity
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 9/14/1998
Publication Date: N/A
Citation: Interpretive Summary: Leptospirosis, caused by infection with bacteria of the genus Leptospira, is an important cause of abortion in livestock and other domestic animals. The bacteria can live in many different sites within the host and in the environment. These sites include blood, kidney tissue, urine, and water or moist soil. We believe that these bacteria produce different proteins and other cellular components during growth in these different environments an that this differential display may be important in the pathogenesis of leptospirosis. In this study, we documented that certain surface components of leptospires are displayed both in culture and in an experimentally infected hamster; other antigens are only displayed in culture. In addition, various leptospiral surface components were shown to be shed from the organism during infection and to localize at sites of inflammation in the kidney. This is the first demonstration of these phenomena with Leptospira and the data suggest that these leptospiral components are involved in the pathogenesis of leptospirosis. In addition, this study provides useful rationale for the selection of bacterial antigens to be used in subunit vaccines.
Technical Abstract: The life cycle of pathogenic Leptospira species includes hematogenous dissemination, kidney infection, and urinary shedding, which facilitates transmission to new hosts. Outer membrane and/or surface components expressed by intraluminal organisms presumably facilitate colonization of the apical surface of proximal renal tubular epithelial cells in the kidney yand may be involved in stimulating the host inflammatory response. Kidney damage resulting from interstitial nephritis is a common complication of leptospirosis. The outer membrane of cultivated Leptospira species contains lipopolysaccharide (LPS), a porin (OmpL1), and the lipoproteins LipL36 and LipL41. Expression and distribution of outer membrane antigens were characterized in a hamster model of leptospirosis. Hamsters were infected by intraperitoneal inoculation with virulent, culture-adapted, or host-adapted L. kirschneri. Serum from hamsters surviving 4 weeks after challenge with culture-adapted L. kirschneri contained antibodies to LPS and all three OMPs; hamsters infected with host-adapted L. kirschneri had no antibody response to LPS or LipL36. Kidney tissue was examined by immunohistochemistry and, at both 10 and 28 days after infection, LPS, OmpL1, and LipL41 were detected on organisms colonizing proximal renal tubules. Although LipL36 is a prominent outer membrane antigen of cultivated L. kirschneri and was detected on cultivated organisms by immunohistochemistry, it could not be detected in vivo. LPS was found throughout the cytoplasm of renal tubular epithelial cells whose surfaces were colonized. In the 28-day kidneys, LPS and OmpL1 were detected in the interstitium and within phagocytes, suggesting that shedding and cellular uptake of the outer membrane antigens contribute to the local host