Brucella and osteoarticular cell activation: partners in crime.

GIAMBARTOLOMEI G. H., ARRIOLA BENITEZ P. C., DELPINO. M. V.

Frontiers in Microbiology

Frontiers Media

Lugar: Lausanne; Año: 2017

Osteoarticularbrucellosis is the most common presentation of human active disease although its reportedprevalence varies widely. The three most common forms ofosteoarticular involvement are sacroiliitis, spondylitis, and peripheralarthritis. Recently the molecular mechanisms implicated in bone damage havebeen started to be elucidated. B. abortusinduces bone damage through diverse mechanisms in which TNF-α and receptor activator of nuclear factorkappa-B ligand (RANKL), the natural modulator of bone homeostasis, are implicated. Theseprocesses are driven by inflammatory cells, including monocytes/macrophages, neutrophils,Th17 CD4+ T and B cells. In addition B. abortus has a direct effect on osteoarticular cells and affects(alters, tilts) homeostatic bone remodeling. The bacterium inhibits bone matrixdeposition by osteoblast (the only bone cells implicated in bone deposition)and modifies the phenotype of these cells to produce matrix methalloproteinases(MMPs) and cytokine secretion that contribute to matrix bone degradation. B. abortus also affects osteoclasts(cells naturally involved in bone resorption) ability by inducing an increasein osteoclastogenesis and osteoclast activation; increasing mineral and organicbone matrix resorption contributing to bone damage. Since the pathology induceby Brucella species involved jointtissue, experiments conducted in sinoviocytes revealed that besides of inducingthe activation of these cells to secrete chemokines, proinflammatory cytokinesand MMPS, the infection also inhibits apoptotic cell death. Brucella is an intracellular bacteriumthat preferentially replicate in endoplasmic reticulum from macrophages. Theanalysis of B. abortus infectedsinoviocytes indicated that bacteria also replicate in the reticulum suggestingthat the bacterium could use this cell type for intracellular replication duringthe osteoarticular localization of the disease. Finally, the molecularmechanisms of osteoarticular brucellosis discovery until now are shedding lighton how interaction of B. abortus withimmune and osteoarticular cells may have an important role in producing damage injoint and bone.