Potential role of fibroblast-like synoviocytes in joint damage induced by Brucella abortus infection through the production and induction of matrix metalloproteinases.

SCIAN ROMINA; BARRIONUEVO PAULA; GIAMBARTOLOMEI GUILLERMO H; DE SIMONE EMILIO; VANZULLI SILVIA; FOSSATI CARLOS A; BALDI PABLO C; DELPINO M VICTORIA

INFECTION AND IMMUNITY

AMER SOC MICROBIOLOGY

Año: 2011 p. 3619 - 3632

0019-9567

Arthritis is one of the most common complications of human brucellosis but its pathogenic mechanisms have not been elucidated. Fibroblast-like synoviocytes (FLS) are known to be central mediators of joint damage in inflammatory arthritides through the production of matrix metalloproteinases (MMPs) that degrade collagen and of cytokines and chemokines that mediate recruitment and activation of leukocytes. In this study we show that Brucella abortus infects and replicates in human FLS (SW982 cell line) in vitro, and that infection results in the production of MMP-2 and proinflammatory mediators (IL-6, IL-8, MCP-1, GM-CSF). Culture supernatants from Brucella-infected FLS induced the migration of monocytes and neutrophils in vitro, and also induced these cells to secrete MMP-9 in a GM-CSF and IL-6 dependent fashion respectively. Reciprocally, culture supernatants from Brucella-infected monocytes and neutrophils induced FLS to produce MMP-2 in a TNF-a dependent fashion. The secretion of proinflammatory mediators and MMP-2 by FLS did not depend on bacterial viability since it was also induced by heat-killed B. abortus (HKBA) and by a model Brucella lipoprotein (L-Omp19). These responses were mediated by recognition of B. abortus antigens through Toll-like receptor 2. Intraarticular injection of HKBA or L-Omp19 in the knee joint of mice resulted in the local induction of proinflammatory mediators, MMP-2 and MMP-9, and in the generation of a mixed inflammatory infiltrate. These results suggest that FLS, and phagocytes recruited by them to the infection focus, may be involved in joint damage during brucellar arthritis through the production of MMPs and proinflammatory mediators.