Natural antibody contributes to host defense against an attenuated Brucella abortus virB mutant.
Brucella abortus is an intracellular pathogen that persists within phagocytic cells of the reticuloendothelial system. To identify in vivo interactions between B. abortus and the host that lead to persistent infection, we studied the persistence of B. abortus and an isogenic virB mutant deficient in the VirB type IV secretion system (T4SS) in knockout mice. In contrast to control mice, mice lacking B cells (Igh6(-/-)) were permissive for infection with the attenuated virB mutant. To determine the basis for this phenotype, we characterized immune functions of Igh6(-/-) mice in the context of B. abortus infection. Igh6(-/-) mice had greater numbers of extracellular bacteria in the spleen and increased early expression of proinflammatory cytokines during B. abortus infection. Further, a virB mutant, despite its wild-type level of survival, failed to elicit microgranuloma formation in the spleens of Igh6(-/-) mice, suggesting a requirement for the T4SS to elicit this pathological change. Passive transfer of immunoglobulin G from naïve mice restored the ability of Igh6(-/-) mice to control the persistence of the virB mutant by a complement-independent mechanism. Further, adoptive transfer of CD11b(+) cells from C57BL/6 mice to Igh6(-/-) mice restored the ability of the knockout mice to limit the replication of the virB mutant in the spleen, suggesting that the Igh6(-)(/)(-) mutation affects phagocyte function and that phagocyte function can be restored by natural antibody.
Department of Medical Microbiology and Immunology, University of California, One Shields Avenue, Davis, California 95616, USA.
Hortensia G
HG
Rolán
Mariana N
MN
Xavier
Renato L
RL
Santos
Renée M
RM
Tsolis
D019264:Adoptive Transfer; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D002003:Brucella abortus / Q000235:genetics / Q000276:immunology*; D002006:Brucellosis / Q000276:immunology* / Q000382:microbiology*; D015169:Colony Count, Microbial; D016207:Cytokines / Q000378:metabolism; D005260:Female; D055786:Gene Knockout Techniques; D006099:Granuloma / Q000276:immunology / Q000382:microbiology; D007116:Immunization, Passive; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D013154:Spleen / Q000382:microbiology / Q000473:pathology; D037521:Virulence Factors / Q000276:immunology*
D000907:Antibodies, Bacterial; D016207:Cytokines; D037521:Virulence Factors