ABSTRACT
Brucella organisms are intracellular parasites of mammals, including humans. Initially bacteria seem to bind lipid rafts and to different membrane receptors of macrophages. In these cells, the cyclic-AMP/protein kinase-A pathway is activated followed by phosphorylation of transcription factors. In epithelial cells, the bacterium activates small GTPases of the Rho subfamily and attains a modest recruitment of actin cytoskeletal structures. In macrophages, most of the ingested Brucella are routed to phagolysosomes and only a few bacteria arrive at endoplasmic reticulum, the compartment that constitutes the Brucella replicating niche. In epithelial cells, on the contrary, most of the bacteria are directed to the endoplasmic reticulum and not to lysosomes. For internalisation, Brucella requires the competence of the BvrS/BvrR regulatory system, while the VirB type IV secretion apparatus is needed for intracellular trafficking. The expression of stationary phase genes seems to be required during the replicating stage. During this period Brucella are able to prevent apoptosis. Replicating bacteria release large quantities of lipopolysaccharide (LPS) within the host cells. The LPS recycles to the cell membrane forming stable complexes with MHC-II proteins in lipid mega-rafts. These surface lipid-LPS-protein macrodomains hamper the presentation of peptides to T-cells. The Brucella LPS also triggers regulatory T cells recognising MHC-II-LPS macrodomains on the surface of antigen presenting cells.
