Leptospiral-induced Murine Chronic Nephritis and Renal Fibrosis Is Enhanced in Absence of Decay-accelerating Factor 1

FERRER MARÍA F.; SCHARRIG EMILIA; LUCRECIA ALBERDI; MAIA CÉDOLA; GABRIELA PRÊTRE; RICARDO DRUT; WEN-CHAO SONG; GÓMEZ RICARDO M.

Ventura, California

Conferencia; Biology of Spirochetes: Unique features of spirochetes- host and environment interactions; 2014

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. Although a few studies in dogs, rats, and even humans have related Leptospira infection and persistence to kidney fibrosis, none have previously characterized this process or studied its occurrence in mice. In the present work, we characterized the acute infection of C57BL/6J mice with a virulent Leptospira interrogans serovar Copenhageni (LIC) strain Fiocruz L1-130 at 14 dpi, its persistence in the kidney by q-PCR and IHC, and its link to kidney fibrosis at 90 dpi. We found that LIC may induce acute moderate nephritis and is able to persist in some animals, inducing fibrosis, as detected by Masson?s trichrome, Picrosirius red staining and q-PCR for collagen I. We then performed a similar study in C57BL/6J Daf1-/- mice, which are well known for their enhanced T-cell hyper-responsiveness. We found that Daf1-/- mice had a lower survival rate, and higher bacterial burden, renal inflammation, and mRNA levels of TGF-β1, IFN-, IL-10, IL-12, IL-13 and IL-17 in the acute stage. However, at the chronic stage, Daf1-/- mice had a lower bacterial burden and lower mRNA cytokine levels, with the exception of IFN-, IL-10, IL-13. In addition, Daf1-/- mice showed higher inflammation and fibrosis at 90 dpi than at 14 dpi and higher levels at all times than the wild-type counterpart. Fibrosis was accompanied by high levels of expression of α-smooth muscle actin and galectin-3. The present study characterizes for the first time, in a mouse experimental model of Leptospira infection, the link between bacterial-induced chronic nephritis with renal fibrosis and how the absence of Daf1 enhances the fibrotic process.