Inflammatory and immunometabolic consequences of gut dysfunction in HIV: Parallels with IBD and implications for reservoir persistence and non-AIDS comorbidities

Jehad Alzahrani, Tabinda Hussain, David Simar, Riya Palchaudhuri, Mohamed Abdel-Mohsen, Suzanne M. Crowe, George W. Mbogo, Clovis S. Palmer*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

58 Scopus citations

Abstract

The gastrointestinal mucosa is critical for maintaining the integrity and functions of the gut. Disruption of this barrier is a hallmark and a risk factor for many intestinal and chronic inflammatory diseases. Inflammatory bowel disease (IBD) and HIV infection are characterized by microbial translocation and systemic inflammation. Despite the clinical overlaps between HIV and IBD, significant differences exist such as the severity of gut damage and mechanisms of immune cell homeostasis. Studies have supported the role of metabolic activation of immune cells in promoting chronic inflammation in HIV and IBD. This inflammatory response persists in HIV+ persons even after long-term virologic suppression by antiretroviral therapy (ART). Here, we review gut dysfunction and microbiota changes during HIV infection and IBD, and discuss how this may induce metabolic reprogramming of monocytes, macrophages and T cells to impact disease outcomes. Drawing from parallels with IBD, we highlight how factors such as lipopolysaccharides, residual viral replication, and extracellular vesicles activate biochemical pathways that regulate immunometabolic processes essential for HIV persistence and non-AIDS metabolic comorbidities. This review highlights new mechanisms and support for the use of immunometabolic-based therapeutics towards HIV remission/cure, and treatment of metabolic diseases.

Original languageEnglish (US)
Pages (from-to)522-531
Number of pages10
JournalEBioMedicine
Volume46
DOIs
StatePublished - Aug 2019

Keywords

  • HIV cure
  • Immunometabolism, microbiome
  • Inflammation
  • Inflammatory bowel disease
  • Macrophage metabolism

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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