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

EBioMedicine. 2019 Aug:46:522-531. doi: 10.1016/j.ebiom.2019.07.027. Epub 2019 Jul 18.

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.

Keywords: HIV cure; Immunometabolism, microbiome; Inflammation; Inflammatory bowel disease; Macrophage metabolism.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Membrane Permeability
  • Comorbidity
  • Dysbiosis
  • Energy Metabolism
  • Fatty Acids / metabolism
  • Gastrointestinal Diseases / etiology*
  • Gastrointestinal Diseases / physiopathology*
  • Gastrointestinal Microbiome / immunology
  • HIV / immunology*
  • HIV Infections / complications
  • HIV Infections / immunology*
  • HIV Infections / metabolism*
  • HIV Infections / virology
  • Humans
  • Inflammatory Bowel Diseases / immunology
  • Inflammatory Bowel Diseases / metabolism
  • Inflammatory Bowel Diseases / pathology
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / microbiology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Monocytes / immunology
  • Monocytes / metabolism

Substances

  • Fatty Acids