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Characterization of recombinant B. abortus strain RB51SOD toward understanding the uncorrelated innate and adaptive immune responses induced by RB51SOD compared to its parent vaccine strain RB51

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dc.contributor.authorZhu, Jianguoen
dc.contributor.authorLarson, Charles B.en
dc.contributor.authorRamaker, Megan Annen
dc.contributor.authorQuandt, Kimberlyen
dc.contributor.authorWendte, Jered M.en
dc.contributor.authorKu, Kimberly P.en
dc.contributor.authorChen, Fangen
dc.contributor.authorJourdian, George W.en
dc.contributor.authorVemulapalli, Rameshen
dc.contributor.authorSchurig, Gerhardt G.en
dc.contributor.authorHe, Yongqunen
dc.date.accessioned2019-11-05T13:49:53Zen
dc.date.available2019-11-05T13:49:53Zen
dc.date.issued2011-11-25en
dc.description.abstractBrucella abortus is a Gram-negative, facultative intracellular pathogen for several mammals, including humans. Live attenuated B. abortus strain RB51 is currently the official vaccine used against bovine brucellosis in the United States and several other countries. Overexpression of protective B. abortus antigen Cu/Zn superoxide dismutase (SOD) in a recombinant strain of RB51 (strain RB51SOD) significantly increases its vaccine efficacy against virulent B. abortus challenge in a mouse model. An attempt has been made to better understand the mechanism of the enhanced protective immunity of RB51SOD compared to its parent strain RB51. We previously reported that RB51SOD stimulated enhanced Th1 immune response. In this study, we further found that T effector cells derived from RB51SOD-immunized mice exhibited significantly higher cytotoxic T lymphocyte activity than T effector cells derived from RB51-immunized mice against virulent B. abortus-infected target cells. Meanwhile, the macrophage responses to these two strains were also studied. Compared to RB51, RB51SOD cells had a lower survival rate in macrophages and induced lower levels of macrophage apoptosis and necrosis. The decreased survival of RB51SOD cells correlates with the higher sensitivity of RB51SOD, compared to RB51, to the bactericidal action of either Polymyxin B or sodium dodecyl sulfate (SDS). Furthermore, a physical damage to the outer membrane of RB51SOD was observed by electron microscopy. Possibly due to the physical damage, overexpressed Cu/Zn SOD in RB51SOD was found to be released into the bacterial cell culture medium. Therefore, the stronger adaptive immunity induced by RB51SOD did not correlate with the low level of innate immunity induced by RB51SOD compared to RB51. This unique and apparently contradictory profile is likely associated with the differences in outer membrane integrity and Cu/Zn SOD release.en
dc.description.notesThis project was supported by NIAID-NIHR-21 grants AI076812 and AI057875 and to Yongqun He. We would like to acknowledge the contributions of Megan Ann Ramaker, Kimberly Quandt, and Jered M. Wendte whose externship in our lab was funded by the University of Michigan Unit for Laboratory Animal Medicine and the American Society of Laboratory Animal Practitioners Foundation. Kimberly P. Ku was supported by the Undergraduate Research Opportunity Program (UROP) at the University of Michigan.en
dc.description.sponsorshipNIAID-NIHR-21 [AI076812, AI057875]; University of Michigan Unit for Laboratory Animal Medicine; American Society of Laboratory Animal Practitioners Foundation; Undergraduate Research Opportunity Program (UROP) at the University of MichiganUniversity of Michigan Systemen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.3389/fcimb.2011.00010en
dc.identifier.issn2235-2988en
dc.identifier.otherUNSP 10en
dc.identifier.pmid22919576en
dc.identifier.urihttp://hdl.handle.net/10919/95254en
dc.identifier.volume1en
dc.language.isoenen
dc.publisherFrontiersen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectBrucella abortus strains RB51 and RB51SODen
dc.subjectCu/Zn superoxide dismutase (Cu/Zn SOD)en
dc.subjectinnate immunityen
dc.subjectadaptive immunityen
dc.subjectcytotoxic T lymphocyte (CTL)en
dc.subjectmacrophage cell deathen
dc.subjectouter membrane integrityen
dc.subjectprotein releaseen
dc.titleCharacterization of recombinant B. abortus strain RB51SOD toward understanding the uncorrelated innate and adaptive immune responses induced by RB51SOD compared to its parent vaccine strain RB51en
dc.title.serialFrontiers in Cellular and Infection Microbiologyen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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