Leptospira interrogans triggers murine kidney fibrosis independently of macrophages and galectin 3

FERRER MF; GOMEZ RM; SCHARRIG E

Mar del Plata

Congreso; LXIV REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA; 2016

Leptospirosis is an emergent zoonotic disease worldwide distributed caused by spirochetes of the genus Leptospira. Macrophage influx and galectin 3 production have been suggested as major players driving acute inflammation and chronic fibrosis in many diseases. However, their involvement in the pathogenesis of Leptospira interrogans serovoar Copenhageni (LIC)-induced renal nephritis and fibrosis are unknown. Our aim was to characterize the role of macrophages and galectin 3 on survival, clinical course, bacteremia, bacterial burden (by real-time PCR (qPCR) and immunohistochemistry), acute pathology (by routine histologic techniques and qRT-PCR), and chronic fibrosis (by picrosirius red technique and digital quantification) in LIC-induced interstitial nephritis and fibrosis in the kidney by a comparative study of normal and macrophage-depleted mice or in absence of galectin 3. Our results showed that C57/BL6J mice infected with LIC and depleted of macrophages by liposome-encapsulated clodronate treatment compared with infected untreated mice presented significant higher bacteremia and subacute bacterial burden as well as increased subacute interstitial nephritis and chronic fibrosis, compared with untreated infected mice. In order to study the role of galectin 3 in LIC-induced nephritis and fibrosis, C57BL/6J Lgals3-/- and their control littermate mice were used. Disruption of the galectin 3 gene significantly increased acute bacterial burden as well as acute kidney inflammation compared with C57BL/6J wild-type mice. Also, galectin 3 disruption significantly increased chronic bacterial burden and fibrosis with similar chronic inflammation. Taken together, these results suggest that macrophages and galectin 3 have a role in limiting LIC burden although bacterial presence is more important than macrophage presence, galectin 3 levels and/or inflammatory cell exudate in order to trigger chronic kidney fibrosis.