Active evasion of CTL mediated killing and low quality responding CD8+ T cells contribute to persistence of brucellosis.

PloS One
M A DurwardGary A Splitter

Abstract

Brucellosis is a common zoonotic disease that remains endemic in many parts of the world. Dissecting the host immune response during this disease provides insight as to why brucellosis is often difficult to resolve. We used a Brucella epitope specific in vivo killing assay to investigate the ability of CD8+ T cells to kill targets treated with purified pathogenic protein. Importantly, we found the pathogenic protein TcpB to be a novel effector of adaptive immune evasion by inhibiting CD8+ T cell killing of Brucella epitope specific target cells in mice. Further, BALB/c mice show active Brucella melitensis infection beyond one year, many with previously unreported focal infection of the urogenital area. A fraction of CD8+ T cells show a CD8+ Tmem phenotype of LFA-1hi, CD127hi, KLRG-1lo during the course of chronic brucellosis, while the CD8+ T cell pool as a whole had a very weak polyfunctional cytokine response with diminished co-expression of IFN-γ with TNFα and/or IL-2, a hallmark of exhaustion. When investigating the expression of these 3 cytokines individually, we observed significant IFN-γ expression at 90 and 180 days post-infection. TNFα expression did not significantly exceed or fall below background levels at any time....Continue Reading

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Citations

Feb 5, 2013·Future Microbiology·Anna Martirosyan, Jean-Pierre Gorvel
Oct 16, 2013·Infection and Immunity·Anthony P CannellaJoseph M Vinetz
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May 1, 2021·International Journal of Molecular Sciences·Hanwei JiaoGuojing Gu
Sep 28, 2021·Frontiers in Immunology·Jin LiuIrina Burd

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Methods Mentioned

BETA
dissection
flow cytometry
ion exchange chromatography

Software Mentioned

Prism
FlowJo
GraphPad

Related Concepts

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Brucellosis (ASM)

Brucellosis is a bacterial infection caused by members of the genus brucella and remains one of the world's major zoonotic diseases. Discover the latest research on Brucellosis here.

Brucellosis

Brucellosis is a bacterial infection caused by members of the genus brucella and remains one of the world's major zoonotic diseases. Discover the latest research on Brucellosis here.