Brucella abortus Invasion of Synoviocytes Inhibits Apoptosis and Induces Bone Resorption through RANKL Expression.

SCIAN R; BARRIONUEVO P; RORIGUEZ AM; ARRIOLA BENITEZ PAULA C; GARCIA SAMARTINO C; FOSSATI C A; GIAMBARTOLOMEI GH; DELPINO M V

INFECTION AND IMMUNITY

AMER SOC MICROBIOLOGY

Lugar: Washington; Año: 2013 p. 1940 - 1951

0019-9567

Arthritis is one of the most common complications of human active brucellosis but its pathogenic mechanisms have not been completely elucidated. In this manuscript, we described the role of synoviocytes in the pathogenesis of brucellar arthritis. Our results indicate that B. abortus infection inhibited synoviocyte apoptosis through the upregulation of anti-apoptotic factors (cIAP-2, Clusterin, Livin and P21/CIP/CDNK1A). In contrast, infection did not change the expression of proteins that have been involved in apoptosis induction such as Bad, Bax, cleaved Pro-caspase 3, CytC, TRAIL, among others; or their expression was reduced as occurs in the case of P-p53(S15). In addition, B. abortus infection induced up-regulation of adhesion molecules (CD54 and CD106), and the adhesion of monocytes and neutrophils to infected-synoviocytes was significantly higher than to uninfected cells. Despite this increased adhesion, B. abortus-infected synoviocytes were able to inhibit apoptosis induced by supernatants from B. abortus-infected monocytes and neutrophils.Moreover, B. abortus infection increased soluble and membrane RANKL expression in synoviocytes that further induced monocytes to undergo osteoclastogenesis. The results presented here are shedding light on how the interactions of B. abortus with synovial fibroblasts may have an important role in the pathogenesis of brucellar arthritis.