Sialylation and fucosylation modulate inflammasome-activating eIF2 Signaling and microbial translocation during HIV infection

Leila B. Giron, Ceylan E. Tanes, Mariane H. Schleimann, Phillip A. Engen, Lisa M. Mattei, Alitzel Anzurez, Mohammad Damra, Huanjia Zhang, Kyle Bittinger, Frederic Bushman, Andrew Kossenkov, Paul W. Denton, Hiroaki Tateno, Ali Keshavarzian, Alan L. Landay, Mohamed Abdel-Mohsen

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

An emerging paradigm suggests that gut glycosylation is a key force in maintaining the homeostatic relationship between the gut and its microbiota. Nevertheless, it is unclear how gut glycosylation contributes to the HIV-associated microbial translocation and inflammation that persist despite viral suppression and contribute to the development of several comorbidities. We examined terminal ileum, right colon, and sigmoid colon biopsies from HIV-infected virally-suppressed individuals and found that gut glycomic patterns are associated with distinct microbial compositions and differential levels of chronic inflammation and HIV persistence. In particular, high levels of the pro-inflammatory hypo-sialylated T-antigen glycans and low levels of the anti-inflammatory fucosylated glycans were associated with higher abundance of glycan-degrading microbial species (in particular, Bacteroides vulgatus), a less diverse microbiome, higher levels of inflammation, and higher levels of ileum-associated HIV DNA. These findings are linked to the activation of the inflammasome-mediating eIF2 signaling pathway. Our study thus provides the first proof-of-concept evidence that a previously unappreciated factor, gut glycosylation, is a force that may impact the vicious cycle between HIV infection, microbial translocation, and chronic inflammation.

Original languageEnglish (US)
Pages (from-to)753-766
Number of pages14
JournalMucosal Immunology
Volume13
Issue number5
DOIs
StatePublished - Sep 1 2020

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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