title: Decay-accelerating factor 1 deficiency exacerbates leptospiral-induced murine chronic nephritis and renal fibrosis.
abstract: Leptospirosis is a global zoonosis caused by pathogenic Leptospira, which can colonize the proximal renal tubules and persist for long periods in the kidneys of infected hosts. Here, we characterized the infection of C57BL/6J wild-type and Daf1-/- mice, which have an enhanced host response, with a virulent Leptospira interrogans strain at 14 days post-infection, its persistence in the kidney, and its link to kidney fibrosis at 90 days post-infection. We found that Leptospira interrogans can induce acute moderate nephritis in wild-type mice and is able to persist in some animals, inducing fibrosis in the absence of mortality. In contrast, Daf1-/- mice showed acute mortality, with a higher bacterial burden. At the chronic stage, Daf1-/- mice showed greater inflammation and fibrosis than at 14 days post-infection and higher levels at all times than the wild-type counterpart. Compared with uninfected mice, infected wild-type mice showed higher levels of IL-4, IL-10 and IL-13, with similar levels of α-smooth muscle actin, galectin-3, TGF-β1, IL-17, IFN-γ, and lower IL-12 levels at 90 days post-infection. In contrast, fibrosis in Daf1-/- mice was accompanied by high expression of α-smooth muscle actin, galectin-3, IL-10, IL-13, and IFN-γ, similar levels of TGF-β1, IL-12, and IL-17 and lower IL-4 levels. This study demonstrates the link between Leptospira-induced murine chronic nephritis with renal fibrosis and shows a protective role of Daf1.
authors.affiliation: Instituto de Biotecnología y Biología Molecular, CONICET-UNLP, La Plata, Buenos Aires, Argentina.
authors.forename: María F
authors.initials: MF
authors.lastname: Ferrer
authors.affiliation: Instituto de Biotecnología y Biología Molecular, CONICET-UNLP, La Plata, Buenos Aires, Argentina.
authors.forename: Emilia
authors.initials: E
authors.lastname: Scharrig
authors.affiliation: Instituto de Biotecnología y Biología Molecular, CONICET-UNLP, La Plata, Buenos Aires, Argentina.
authors.forename: Lucrecia
authors.initials: L
authors.lastname: Alberdi
authors.affiliation: Instituto de Biotecnología y Biología Molecular, CONICET-UNLP, La Plata, Buenos Aires, Argentina.
authors.forename: Maia
authors.initials: M
authors.lastname: Cedola
authors.affiliation: Instituto de Biotecnología y Biología Molecular, CONICET-UNLP, La Plata, Buenos Aires, Argentina.
authors.forename: Gabriela
authors.initials: G
authors.lastname: Pretre
authors.affiliation: Cátedra de Patología "A", Facultad de Medicina, UNLP, La Plata, Buenos Aires, Argentina.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Drut
authors.affiliation: Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Wen-Chao
authors.initials: WC
authors.lastname: Song
authors.affiliation: Instituto de Biotecnología y Biología Molecular, CONICET-UNLP, La Plata, Buenos Aires, Argentina.
authors.forename: Ricardo M
authors.initials: RM
authors.lastname: Gomez
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D018958:CD55 Antigens / Q000378:metabolism*; D005355:Fibrosis / Q000378:metabolism* / Q000382:microbiology; D037502:Galectin 3 / Q000378:metabolism; D007249:Inflammation / Q000378:metabolism / Q000382:microbiology; D007371:Interferon-gamma / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D007674:Kidney Diseases / Q000378:metabolism* / Q000382:microbiology; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000382:microbiology; D007921:Leptospira interrogans; D007922:Leptospirosis / Q000378:metabolism* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009393:Nephritis / Q000378:metabolism* / Q000401:mortality; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000199:Actins; D018958:CD55 Antigens; D037502:Galectin 3; D007378:Interleukins; D053773:Transforming Growth Factor beta1; C544013:alpha-smooth muscle actin, mouse; C521184:decay-accelerating factor 1, mouse; D007371:Interferon-gamma