The effect of environmental pollution on immune evasion checkpoints of SARS-CoV-2

Environ Toxicol Pharmacol. 2021 Jan;81:103520. doi: 10.1016/j.etap.2020.103520. Epub 2020 Oct 22.


Many diverse strategies allow and facilitate severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to evade antiviral innate immune mechanisms. Although the type I interferon (IFN) system has a critical role in restricting the dissemination of viral infection, suppression of IFN receptor signals by SARS-CoV-2 constitutes a checkpoint that plays an important role in the immune escape of the virus. Environmental pollution not only facilitates SARS-CoV-2 infection but also increases infection-associated fatality risk, which arises due to Systemic Aryl hydrocarbon Receptor (AhR) Activation Syndrome. The intracellular accumulation of endogenous kynurenic acid due to overexpression of the indoleamine 2,3-dioxygenase (IDO) by AhR activation induces AhR-interleukin-6 (IL-6)-signal transducers and activators of the transcription 3 (STAT3) signaling pathway. The AhR-IDO1-Kynurenine pathway is an important checkpoint, which leads to fatal consequences in SARS-CoV-2 infection and immune evasion in the context of Treg/Th17 imbalance and cytokine storm.

Keywords: Angiotensin-converting enzyme 2; Aryl hydrocarbon receptor; Environmental pollution; Indoleamine 2,3-dioxygenase; Interferons; Severe acute respiratory syndrome coronavirus 2.

Publication types

  • Review

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • COVID-19 / immunology*
  • COVID-19 / metabolism
  • COVID-19 Drug Treatment
  • Environmental Pollution / adverse effects*
  • Humans
  • Immune Evasion / drug effects
  • Immune Evasion / immunology*
  • Immunity, Innate / drug effects
  • Immunity, Innate / immunology*
  • Inflammation Mediators / immunology*
  • Inflammation Mediators / metabolism
  • Receptors, Aryl Hydrocarbon / immunology
  • Receptors, Aryl Hydrocarbon / metabolism


  • Antiviral Agents
  • Inflammation Mediators
  • Receptors, Aryl Hydrocarbon