Pathogenesis and pathobiology of zoonotic brucellosis in humans

Abstract

Although human brucellosis has protean clinical manifestations, affected tissues usually exhibit signs of inflammation. The cellular and molecular bases of some immunopathological phenomena probably involved in the pathogenesis of infection with brucellae have been elucidated recently. Human osteoblasts and fibroblast-like synoviocytes produce cytokines, chemokines and matrix metalloproteinases in response to infection with brucellae and/or to stimulation by brucellae-infected monocytes. In turn, released cytokines promote the secretion of the metalloproteinases and induce osteoclastogenesis. These phenomena may underlie the bone loss and cartilage degradation found in brucellar arthritis and osteomyelitis. Brucella abortus and its lipoproteins elicit an inflammatory response in the central nervous system of mice, leading to astrogliosis, a characteristic feature of neurobrucellosis. Brucellae can also replicate in human endothelial cells, inducing an inflammatory response with increased expression of chemokines, interleukin-6 and adhesion molecules. Persistent brucellar infection of the endothelium would support development of endocarditis and other vascular manifestations. Thus, although the inflammatory phenomena triggered by brucellae are relatively mild, they are long-lasting as a result of the prolonged intracellular persistence of the bacteria in infected tissues and eventually lead to tissue damage.