Interaction of Brucella suis and Brucella abortus rough strains with human dendritic cells.
Brucella is a facultative intracellular pathogen of various mammals and the etiological agent of brucellosis. We recently demonstrated that dendritic cells (DCs), which are critical components of adaptive immunity, are highly susceptible to Brucella infection. Furthermore, Brucella prevented the infected DCs from engaging in maturation processes and impaired their capacity to present antigen to naive T cells and to secrete interleukin-12 (IL-12). The lipopolysaccharide (LPS) phenotype is largely associated with the virulence of Brucella. Depending on whether they express the O-side chain of LPS or not, the bacteria display a smooth or rough phenotype. Rough Brucella mutants are attenuated and induce a potent protective T-cell-dependent immune response. Due to the essential role of DCs in the initiation of T-cell-dependent adaptive immune responses, it seemed pertinent to study the interaction between rough Brucella strains and human DCs. In the present paper, we report that, in contrast to smooth bacteria, infection of DCs with rough mutants of Brucella suis or Brucella abortus leads to both phenotypic and functional maturation of infected cells. Rough mutant-infected DCs then acquire the capacity to produce IL-12 and to stimulate naive CD4+ T lymphocytes. Experiments with rough and smooth purified LPS of Brucella supported the hypothesis of an indirect involvement of the O-side chain. These results provide new data concerning the role of LPS in Brucella virulence strategy and illuminate phenomena contributing to immune protection conferred by rough vaccine strains.
Billard
Elisabeth
E
Université Montpellier 1, Centre d'étude d'agents Pathogènes et Biothechnologies pour la Santé, Montpellier, France.
Dornand
Jacques
J
Gross
Antoine
A
D002003:Brucella abortus / Q000276:immunology*; D041021:Brucella suis / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000382:microbiology; D006801:Humans; D018664:Interleukin-12 / Q000276:immunology; D008070:Lipopolysaccharides / Q000737:chemistry / Q000276:immunology; D019081:O Antigens / Q000737:chemistry / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology
D008070:Lipopolysaccharides; D019081:O Antigens; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12