Title:Immunopathology of Brucella Infection
Volume: 8
Issue: 1
Author(s): Pablo C. Baldi and Guillermo H. Giambartolomei
Affiliation:
Keywords:
Astrogliosis, bacterial lipoproteins, cytokines, inflammation, matrix metalloproteinases, osteoclastogenesis, TLR2, Neurobrucellosis, osteomyelitis, lipopolysaccharide
Abstract: In spite of the protean nature of the disease, inflammation is a hallmark of brucellosis and affected tissues usually
exhibit inflammatory infiltrates. As Brucella lacks exotoxins, exoproteases or cytolysins, pathological findings in
brucellosis probably arise from inflammation-driven processes. The cellular and molecular bases of immunopathological
phenomena probably involved in Brucella pathogenesis have been unraveled in the last few years. Brucella-infected osteoblasts,
either alone or in synergy with infected macrophages, produce cytokines, chemokines and matrixmetalloproteinases
(MMPs), and similar phenomena are mounted by fibroblast-like synoviocytes. The released cytokines
promote the secretion of MMPs and induce osteoclastogenesis. Altogether, these phenomena may contribute to the bone
loss and cartilage degradation usually observed in brucellar arthritis and osteomyelitis. Proinflammatory cytokines may be
also involved in the pathogenesis of neurobrucellosis. B. abortus and its lipoproteins elicit an inflammatory response in
the CNS of mice, leading to astrogliosis, a characteristic feature of neurobrucellosis. Heat-killed bacteria (HKBA) and the
L-Omp19 lipoprotein elicit astrocyte apoptosis and proliferation (two features of astrogliosis), and apoptosis depends on
TNF-α signaling. Brucella also infects and replicates in human endothelial cells, inducing the production of chemokines
and IL-6, and an increased expression of adhesion molecules. The sustained inflammatory process derived from the longlasting
infection of the endothelium may be important for the development of endocarditis. Therefore, while Brucella induces
a low grade inflammation as compared to other pathogens, its prolonged intracellular persistence in infected tissues
supports a long-lasting inflammatory response that mediates different pathways of tissue damage. In this context, approaches
to avoid the invasion of host cells or limit the intracellular survival of the bacterium may be suitable to prevent
the pathological consequences of Brucella infections. The article presents some of the recent patents related to such approaches.