title: A B lymphocyte mitogen is a Brucella abortus virulence factor required for persistent infection.
abstract: Microbial pathogens with the ability to establish chronic infections have evolved strategies to actively modulate the host immune response. Brucellosis is a disease caused by a Gram-negative intracellular pathogen that if not treated during the initial phase of the infection becomes chronic as the bacteria persist for the lifespan of the host. How this pathogen and others achieve this action is a largely unanswered question. We report here the identification of a Brucella abortus gene (prpA) directly involved in the immune modulation of the host. PrpA belongs to the proline-racemase family and elicits a B lymphocyte polyclonal activation that depends on the integrity of its proline-racemase catalytic site. Stimulation of splenocytes with PrpA also results in IL-10 secretion. Construction of a B. abortus-prpA mutant allowed us to assess the contribution of PrpA to the infection process. Mice infected with B. abortus induced an early and transient nonresponsive status of splenocytes to both Escherichia coli LPS and ConA. This phenomenon was not observed when mice were infected with a B. abortus-prpA mutant. Moreover, the B. abortus-prpA mutant had a reduced capacity to establish a chronic infection in mice. We propose that an early and transient nonresponsive immune condition of the host mediated by this B cell polyclonal activator is required for establishing a successful chronic infection by Brucella.
authors.affiliation: Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico Chascomús, Universidad Nacional de San Martín, Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina, Avenida General Paz 5445, 1650 San Martín, Argentina.
authors.forename: Juan Manuel
authors.initials: JM
authors.lastname: Spera
authors.forename: Juan Esteban
authors.initials: JE
authors.lastname: Ugalde
authors.forename: Juan
authors.initials: J
authors.lastname: Mucci
authors.forename: Diego J
authors.initials: DJ
authors.lastname: Comerci
authors.forename: Rodolfo Augusto
authors.initials: RA
authors.lastname: Ugalde
mesh_terms: D000591:Amino Acid Isomerases / Q000145:classification / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism* / Q000821:virology; D001665:Binding Sites; D002003:Brucella abortus / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002006:Brucellosis / Q000276:immunology / Q000473:pathology* / Q000821:virology*; D005260:Female; D016753:Interleukin-10 / Q000378:metabolism; D008561:Membrane Fusion; D051379:Mice; D008807:Mice, Inbred BALB C; D008938:Mitosis; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D037521:Virulence Factors / Q000145:classification / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D037521:Virulence Factors; D016753:Interleukin-10; D000591:Amino Acid Isomerases; C022451:proline racemase