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ARS Home » Midwest Area » Ames, Iowa » National Animal Disease Center » Infectious Bacterial Diseases Research » Research » Publications at this Location » Publication #355132

Research Project: Characterization of the Pathogenesis and Antigen Expression in Spirochete Diseases

Location: Infectious Bacterial Diseases Research

Title: Macrophages and galectin 3 control bacterial burden in acute and subacute murine leptospirosis that determines chronic kidney fibrosis

Author
item Ferrer, Maria - Institute Of Biotechnology And Molecular Biology (IBBM)
item Scharrig, Emilia - Institute Of Biotechnology And Molecular Biology (IBBM)
item Charo, Nancy - The Experimental Medicine And Biology Institute(IBYME)
item Ripodas, Ana - Bio Lab
item Drut, Ricardo - Children'S Hospital Sister Maria Ludovica
item Carrera Silva, Eugenio - Institute Of Biotechnology And Molecular Biology (IBBM)
item Nagel, Ariel - Institute Of Biotechnology And Molecular Biology (IBBM)
item Nally, Jarlath
item Montes De Oca, Daniela - Ifibyne (UBA-CONICET)
item Schattner, Mirta - Institute Of Biotechnology And Molecular Biology (IBBM)
item Gomez, Ricardo - Institute Of Biotechnology And Molecular Biology (IBBM)

Submitted to: Frontiers in Cellular and Infection Microbiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/11/2018
Publication Date: 10/30/2018
Citation: Ferrer, M.F., Scharrig, E., Charo, N., Ripodas, A.L., Drut, R., Carrera Silva, E.A., Nagel, A., Nally, J.E., Montes De Oca, D.P., Schattner, M., Gomez, R.M. 2018. Macrophages and galectin 3 control bacterial burden in acute and subacute murine leptospirosis that determines chronic kidney fibrosis. Frontiers in Cellular and Infection Microbiology. doi:10.3389/fcimb.2018.00384.
DOI: https://doi.org/10.3389/fcimb.2018.00384

Interpretive Summary: Pathogenic species of Leptospira cause leptospirosis, a global disease that is transmitted from animals to humans. Leptospires survive in the kidney of domestic and wild animal species, which act as reservoir hosts of infection, and excrete leptospires via urine. Reservoir hosts of leptospirosis are typically asymptomatic and can excrete leptospires for months and years. A unique biological equilibrium exists between pathogenic leptospires and reservoir hosts of infection, but surprisingly, little is known concerning the host’s cellular immune response that facilitates this persistent renal colonization. A mouse and rat model of infection was used to address the role of macrophages during the initial stages of infection and dissemination, and its subsequent involvement in kidney fibrosis and bacterial load. Our results demonstrate that macrophages play a critical role in controlling the burden of leptospires in host tissue, but a minor role in subsequent fibrosis. Instead, kidney fibrosis was better correlated with bacterial burden.

Technical Abstract: Previous studies have suggested that macrophages may contribute to acute Leptospira dissemination, as well as having a major role in kidney fibrosis. Our aim was to characterise the role of macrophages and galectin 3 (Gal-3) on the survival, clinical course, bacterial burden, interstitial nephritis, and chronic kidney fibrosis in Leptospira interrogans serovar Copenhageni (LIC)-induced experimental murine leptospirosis. C57BL/6J mice depleted of macrophages by liposome-encapsulated clodronate treatment and infected with LIC presented a higher bacterial burden, had reduced subacute nephritis and enhanced chronic kidney fibrosis relative to untreated, infected mice. Moreover, LIC infection in mice whose Gal-3 was disrupted (Lgals3-/-) had a higher bacterial burden and enhanced subacute nephritis and chronic kidney fibrosis when compared to C57BL/6J wild-type mice. Chronic fibrosis did not correlate with higher transcription levels of TGF-ß1 or IL-13 in the kidneys. Kidney fibrosis was found in chronically infected rats as well as in wild infected rats. On the other hand, human fibroblast cultures exhibited enhanced differentiation to myofibroblasts after treatment with LIC. Our results demonstrate that macrophages and Gal-3 play a critical role in controlling the LIC burden but has a minor role in subsequent fibrosis. Instead, kidney fibrosis was better correlated with bacterial burden. Taken together, our results do not support a role for macrophages to disseminate leptospires during acute infection, nor in chronic kidney fibrosis.