title: A Brucella virulence factor targets macrophages to trigger B-cell proliferation.
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.
authors.affiliation: Instituto de Investigaciones Biotecnológicas Dr. Rodolfo A. Ugalde, IIB-INTECH, National Research Council of Argentina (CONICET), Universidad Nacional de San Martín, San Martín 1650, Buenos Aires, Argentina.
authors.forename: Juan M
authors.initials: JM
authors.lastname: Spera
authors.forename: Claudia K
authors.initials: CK
authors.lastname: Herrmann
authors.forename: Mara S
authors.initials: MS
authors.lastname: Roset
authors.forename: Diego J
authors.initials: DJ
authors.lastname: Comerci
authors.forename: Juan E
authors.initials: JE
authors.lastname: Ugalde
mesh_terms: D000591:Amino Acid Isomerases / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology*; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015153:Blotting, Western; D002003:Brucella abortus / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D005260:Female; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008856:Microscopy, Fluorescence; D024507:Nonmuscle Myosin Type IIA / Q000276:immunology / Q000378:metabolism; D011485:Protein Binding; D015800:Protozoan Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000276:immunology / Q000378:metabolism / Q000472:pathogenicity; D014774:Virulence / Q000276:immunology; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D015800:Protozoan Proteins; D037521:Virulence Factors; D024507:Nonmuscle Myosin Type IIA; D000591:Amino Acid Isomerases
keywords: Bacteria; Brucella; Lymphocyte; Macrophages; Myosin; Virulence Factors