Brucella alters the immune response in a prpA-dependent manner

SPERA JM; COMERCI DJ; UGALDE JE

MICROBIAL PATHOGENESIS

ACADEMIC PRESS LTD-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2014

0882-4010

Brucellosis is a widespread zoonosis still endemic in many areas of the world that inflicts important animal and human health problems, especially in developing countries. One of the hallmarks of Brucella infection is its capacity to establish a chronic infection, characteristic that depends on a plethora of virulence factors with immunomodulatory activities. One of such factors is PrpA, an effector that targets macrophages to trigger B-cell polyclonal activation in vitro and is involved in the establishment of a chronic infection. B-lymphocytes, opsonizing antibodies and cytokines are three central functions of the immune system necessary to control infections. We report here that Brucella abortus subverts these functions as a virulence strategy. We show that, in vivo, B. abortus virulence factor prpA is responsible for an increment in the B-cell number and the specific antibody response and that these antibodies promote cell infection. In order to determine if PrpA also modulates the cytokine response in vivo we measured several important cytokines during the infection with the prpA deletion mutant and found that IFN-γ, IL-10, TGFβ and TNFα are altered during the acute phase of the infectious process. We demonstrated that, while the canonical pro-inflammatory cytokines IFNγ and TNFα were significantly upregulated in the mutant, the case of two central anti-inflammatory cytokines, IL-10 and TGFβ showed opposite patterns of secretion. The possible consequences of these prpA-mediated immune alterations are discussed.