Abstract
Brucella spp. and Trypanosoma cruzi are two intracellular pathogens that have no evolutionary common origins but share a similar lifestyle as they establish chronic infections for which they have to circumvent the host immune response. Both pathogens have a virulence factor (prpA in Brucella and tcPrac in T. cruzi) that induces B-cell proliferation and promotes the establishment of the chronic phase of the infectious process. We show here that, even though PrpA promotes B-cell proliferation, it targets macrophages in vitro and is translocated to the cytoplasm during the intracellular replication phase. We observed that PrpA-treated macrophages induce the secretion of a soluble factor responsible for B-cell proliferation and identified nonmuscular myosin IIA (NMM-IIA) as a receptor required for binding and function of this virulence factor. Finally, we show that the Trypanosoma cruzi homologue of PrpA also targets macrophages to induce B-cell proliferation through the same receptor, indicating that this virulence strategy is conserved between a bacterial and a protozoan pathogen.
Highlights
PrpA is a Brucella B-cell lymphoproliferative virulence factor
We have previously described a B-lymphocyte mitogen in Brucella abortus (PrpA,4 for proline racemase protein A) that induces a transient nonresponsive state of splenocytes, acts as a potent IL-10 inducer, and participates in the efficient establishment of a chronic infection in mice [7]
We report here that PrpA targets macrophages and that it binds to nonmuscular myosin IIA (NMM-IIA) in vitro and during the infection of cells and that this binding triggers B-cell proliferation via a yet unidentified soluble factor
Summary
PrpA is a Brucella B-cell lymphoproliferative virulence factor. Results: PrpA and its homologue in Trypanosoma cruzi bind to macrophages through nonmuscular myosin IIA (NMM-IIA) to trigger B-cell proliferation. Brucella spp. and Trypanosoma cruzi are two intracellular pathogens that have no evolutionary common origins but share a similar lifestyle as they establish chronic infections for which they have to circumvent the host immune response. Both pathogens have a virulence factor (prpA in Brucella and tcPrac in T. cruzi) that induces B-cell proliferation and promotes the establishment of the chronic phase of the infectious process.
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