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Wilson lab reports in Mucosal Immunology that gut dendritic cell activation links an altered colonic microbiome to mucosal and systemic T-cell activation in untreated HIV-1 infection

HIV-1-associated disruption of intestinal homeostasis is a major factor contributing to chronic immune activation and inflammation. Dendritic cells (DCs) are crucial in maintaining intestinal homeostasis, but the impact of HIV-1 infection on intestinal DC number and function has not been extensively studied.

 

     In the April 29, 2015 issue of Mucosal Immunology, Stephanie Dillon and coworkers in Cara Wilson’s lab address this issue. They compared the frequency and activation/maturation status of colonic myeloid DC (mDC) subsets (CD1c+ and CD1cneg) and plasmacytoid DCs in untreated HIV-1-infected subjects with uninfected controls. Colonic mDCs in HIV-1-infected subjects had increased CD40 but decreased CD83 expression, and CD40 expression on CD1c+ mDCs positively correlated with mucosal HIV-1 viral load, with mucosal and systemic cytokine production, and with frequencies of activated colon and blood T cells. Percentage of CD83+CD1c+ mDCs negatively correlated with frequencies of interferon-γ-producing colon CD4+ and CD8+ T cells. CD40 expression on CD1c+ mDCs positively associated with abundance of high prevalence mucosal Prevotella copri and Prevotella stercorea but negatively associated with a number of low prevalence mucosal species, including Rumminococcus bromii. CD1c+ mDC cytokine production was greater in response to in vitro stimulation with Prevotella species relative to R. bromii.

 

   These findings suggest that, during HIV infection, colonic mDCs become activated upon exposure to mucosal pathobiont bacteria leading to mucosal and systemic immune activation.

 

 

This study was supported by National Institutes of Health Grants RO1 DK088663 (Wilson), R01 AI108404 (Wilson) and, in part, by NIH/NCATS Colorado CTSI Grant Number UL1 TR000154.  Co-authors include CU Department of Medicine researchers Cassie Kotter, Greg Austin, Martine McManus, Chuck Robertson, Dan Frank and Martin McCarter as well as collaborators at Rush University Medical Center, Chicago and University of California San Diego, California.