Decay-accelerating factor 1 deficiency exacerbates leptospiral-induced murine chronic nephritis and renal fibrosis

MARIA F. FERRER; EMILIA SCHARRIG; LUCRECIA ALBERDI; MAIA CEDOLA; GABRIELA PRETRE; RICARDO DRUT; WEN-CHAO SONG; RICARDO M. GOMEZ

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2014 vol. 9 p. 102860 - 102861

1932-6203

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-/- 29 mice showed acute mortality, with a higher bacterial burden and renal inflammation. 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 a-smooth muscle actin, galectin-3, TGF-b1, IL-17, IFN-g, and lower IL-12 levels at 90 days post-infection. In contrast, fibrosis in Daf1-/- mice was accompanied by high expression of a-smooth muscle actin, galectin-3, IL-10, IL-13, and IFN-g, similar levels of TGF-b1, 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.