Macrophages and Galectin 3 Control Bacterial Burden in Acute and Subacute Murine Leptospirosis That Determines Chronic Kidney Fibrosis

FERRER, MARÍA F.; SCHARRIG, EMILIA; CHARO, NANCY; RÍPODAS, ANA L.; DRUT, RICARDO; CARRERA SILVA, EUGENIO A.; NAGEL, ARIEL; NALLY, JARLATH E.; MONTES DE OCA, DANIELA P.; SCHATTNER, MIRTA; GÓMEZ, RICARDO M.

Frontiers in Cellular and Infection Microbiology

Frontiers Editorial Office

Año: 2018 vol. 8

Previous studies have suggested that macrophages may contribute to acute Leptospiradissemination, as well as having a major role in kidney fibrosis. Our aim was tocharacterize the role of macrophages and galectin 3 (Gal-3) on the survival, clinicalcourse, bacterial burden, interstitial nephritis, and chronic kidney fibrosis in Leptospirainterrogans serovar Copenhageni (LIC)-induced experimental murine leptospirosis.C57BL/6J mice depleted of macrophages by liposome-encapsulated clodronatetreatment and infected with LIC presented a higher bacterial burden, had reducedsubacute nephritis and enhanced chronic kidney fibrosis relative to untreated, infectedmice. Moreover, LIC infection in mice whose Gal-3 was disrupted (Lgals3−/?) had ahigher bacterial burden and enhanced subacute nephritis and chronic kidney fibrosiswhen compared to C57BL/6J wild-type mice. Chronic fibrosis did not correlate withhigher transcription levels of TGF-b1 or IL-13 in the kidneys. Kidney fibrosis was foundin chronically infected rats as well as in wild infected rats. On the other hand, humanfibroblast cultures exhibited enhanced differentiation to myofibroblasts after treatmentwith LIC. Our results demonstrate that macrophages and Gal-3 play a critical role incontrolling the LIC burden but has a minor role in subsequent fibrosis. Instead, kidneyfibrosis was better correlated with bacterial burden. Taken together, our results do notsupport a role for macrophages to disseminate leptospires during acute infection, nor inchronic kidney fibrosis.