Highly Human Immunodeficiency Virus-Exposed Seronegative Men Have Lower Mucosal Innate Immune Reactivity

AIDS Research and Human Retroviruses
Jennifer A FulcherOtto O Yang

Abstract

Risk of HIV acquisition varies, and some individuals are highly HIV-1-exposed, yet, persistently seronegative (HESN). The immunologic mechanisms contributing to this phenomenon are an area of intense interest. As immune activation and inflammation facilitate disease progression in HIV-1-infected persons and gastrointestinal-associated lymphoid tissue is a highly susceptible site for transmission, we hypothesized that reduced gut mucosal immune reactivity may contribute to reduced HIV-1 susceptibility in HESN men with a history of numerous rectal sexual exposures. To test this, we used ex vivo mucosal explants from freshly acquired colorectal biopsies from healthy control and HESN subjects who were stimulated with specific innate immune ligands and inactivated whole pathogens. Immune reactivity was then assessed via cytokine arrays and proteomic analysis. Mucosal immune cell compositions were quantified via immunohistochemistry. We found that explants from HESN subjects produced less proinflammatory cytokines compared with controls following innate immune stimulation; while noninflammatory cytokines were similar between groups. Proteomic analysis identified several immune response proteins to be differentially expressed between ...Continue Reading

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Citations

Nov 27, 2019·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Christophe VanpouilleSara Gianella

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Methods Mentioned

BETA
nucleic acid amplification
biopsies
biopsy
transfection

Software Mentioned

Mascot
GraphPad Prism
Progenesis QI - P
DAVID Bioinformatics Resources
GraphPad
Proteome
Scaffold
Mascot Daemon

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