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

Authors

Leila B. Giron, The Wistar Institute
Ceylan E. Tanes, Children's Hospital of Philadelphia
Mariane H. Schleimann, Aarhus University
Phillip A. Engen, Rush University Medical Center
Lisa M. Mattei, Children's Hospital of Philadelphia
Altizel Anzurez, The Wistar Institute
Mohammad Damra, The Wistar Institute
Huanjia Zhang, Children's Hospital of Philadelphia
Kyle Bittinger, Children's Hospital of Philadelphia
Frederic Bushman, University of Pennsylvania
Andrew Kossenkov, The Wistar Institute
Paul Denton, University of Nebraska at OmahaFollow
Hiroaki Tateno, National Institute of Advanced Industrial Science and Technology (AIST)
Ali Keshavarizian, Rush University Medical Center
Mohamed Abdel-Mohsen, The Wistar Institute
Alan L. Landay, Rush University Medical Center

Author ORCID Identifier

Denton - https://orcid.org/0000-0003-2458-8147

Document Type

Article

Publication Date

12-31-2022

Publication Title

Mucosal Immunology

Volume

13

Issue

5

First Page

753

Last Page

766

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.

Comments

This is an open access article licensed under the Creative Commons Attribution license.

DOI: https://doi.org/10.1038/s41385-020-0279-5

Recommended Citation

Giron, Leila B.; Tanes, Ceylan E.; Schleimann, Mariane H.; Engen, Phillip A.; Mattei, Lisa M.; Anzurez, Altizel; Damra, Mohammad; Zhang, Huanjia; Bittinger, Kyle; Bushman, Frederic; Kossenkov, Andrew; Denton, Paul; Tateno, Hiroaki; Keshavarizian, Ali; Abdel-Mohsen, Mohamed; and Landay, Alan L., "Sialylation and fucosylation modulate inflammasome-activating eIF2 Signaling and microbial translocation during HIV infection" (2022). Biology Faculty Publications. 184.
https://digitalcommons.unomaha.edu/biofacpub/184

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.