Skewed CD39/CD73/adenosine pathway in B cells is associated with innate immune hyperactivation in chronic HIV-1 infection View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2019-12

AUTHORS

Wen-Xian Chang, Hui-Huang Huang, Lei Huang, Ji-Jing Shi, Yan-Mei Jiao, Chao Zhang, Lei Jin, Tao Yang, Ming Shi, Bo Tu, Zhe Xu, Tian-Jun Jiang, Fu-Sheng Wang, Ji-Yuan Zhang

ABSTRACT

The CD39/CD73/adenosine suppression pathway correlates with disease progression in patients with chronic human immunodeficiency virus 1 (HIV-1) infection; however, the relationships between this pathway in B cells and innate immune hyperactivation remain largely undefined. In this study, we examined CD39 and CD73 expression, and adenosine production by B cells from 136 patients with chronic HIV-1 infection. The CD39 and CD73 expression levels on total B cells (and their subsets) decreased continuously in typical progressors (TPs), but were gradually recovered in complete responders. In TPs, the frequencies of CD39+, CD73+, and CD39+CD73+ B cells inversely correlated with HIV-1 viral load and positively correlated with CD4 T cell counts, but also positively associated with CD4/CD8 ratioes and inversely correlated with markers for intestinal epithelial injury and microbial translocation. Furthermore, B cells from TPs showed a markedly reduced capacity to generate CD39/CD73-dependent extracellular adenosine; the loss of this capacity was more serious in patients with acquired immunodeficiency syndrome. In vitro, increased adenosine could inhibit the activation of monocytes and suppress the ability of monocytes and T cells to produce TNF-alpha, regardless of their infection status. Moreover, adenosine could inhibit activation-induced HIV-1 virion production and p24 expression. These findings provided a new role of B cell pathology in HIV-1 infection, in which the skewed CD39/CD73/adenosine pathway in B cells linked to microbial translocation-induced innate immune hyperactivation, supporting the notion that regulating the adenosine pathway in B cells might be an attractive approach to treat patients with HIV-1-infection. More... »

PAGES

4

References to SciGraph publications

Identifiers

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http://scigraph.springernature.com/pub.10.1186/s41231-019-0033-8

DOI

http://dx.doi.org/10.1186/s41231-019-0033-8

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https://app.dimensions.ai/details/publication/pub.1112119194


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