Abstract/Details

B lymphocytes promote the establishment of the plateau phase of brucellosis


2008 2008

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Abstract (summary)

Brucella abortus is a facultative intracellular gram-negative bacterium that causes chronic protracted infections of humans and livestock. It is also a potential biowarfare agent and thus development of vaccines for humans is an important goal. In mice infected with Brucella abortus, protective roles for CD4 and CD8 T cells have been demonstrated. A critical role for T cells is likely to be production of IFNγ as IFNγ-deficient mice succumb to brucellosis. Here we show both T cell subsets contribute to control of infection by virulent strain B. abortus 2308 by producing IFNγ and CD4 T cells but not CD8 T cells facilitate clearance of infection. Strikingly, antibody-independent B cell functions contribute to the development of the high plateau phase of infection as both B cell/antibody-deficient C57BL/6 and BALB/c mice cleared 99% of the infection by 2 weeks in an antibody-independent manner. Further characterization of the immune response revealed that B cells produced regulatory cytokines in both C57BL/6 and BALB/c mice. B cells from C57BL/6 mice produced IL-10 while B cells from BALB/c mice produced TGF-β, which in turn can dampen protective IFN-γ mediated immune responses. Consequently, clearance of infection in B cell deficient C57BL/6 mice coincided with a decrease in IL-10 and an increase in the proportion of IFNγ-producing T cells while the clearance of infection in B cell deficient BALB/c mice was associated with a decrease in TGF-β producing cells and CD4 T regulatory cells. Due to the rapid clearance of infection in B cell deficient mice, we tested whether B lymphocytes act as an infection niche for brucellae and found that IgM and complement-opsonized viable B. abortus were phagocytosed by and survived within B lymphocytes in vitro. Furthermore, live brucellae were harbored within B lymphocytes in infected mice and these cells transferred disease to uninfected animals. Throughout the infection, a greater proportion of infected B lymphocytes produced TGFβ compared to non-infected B cells. Thus, B lymphocytes contribute to chronic brucellosis, and possibly other diseases, by providing an intracellular niche that can shield the bacteria from the host immune system and dampen inflammatory responses needed to clear the infection.

Indexing (details)


Subject
Veterinary services
Classification
0778: Veterinary services
Identifier / keyword
Biological sciences, B lymphocytes, Brucella abortus, Brucellosis, IFN gamma, Plateau phase, TGF-beta
Title
B lymphocytes promote the establishment of the plateau phase of brucellosis
Author
Goenka, Radhika
Number of pages
135
Publication year
2008
Degree date
2008
School code
0118
Source
DAI-B 69/07, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9780549728900
Advisor
Baldwin, Cynthia L.
Committee member
Black, Samuel J.; Webley, Wilmore C.
University/institution
University of Massachusetts Amherst
Department
Animal Science
University location
United States -- Massachusetts
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3322188
ProQuest document ID
89269137
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/89269137
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