Arginase and its mechanisms in Leishmania persistence

Parasite Immunol. 2020 Jul;42(7):e12722. doi: 10.1111/pim.12722.

Abstract

Leishmaniasis is a neglected infectious disease with clinical presentations ranging from asymptomatic or mild symptoms to chronic infection and eventual death. The mechanisms of disease susceptibility and pathology have been extensively studied, but there are no steadfast rules regarding leishmaniasis. A Th1 response is usually associated with infection control, while a predominant Th2 response is detrimental to the patient. In this scenario, the enzymes arginase and inducible nitric oxide synthase represent two possible pathways of immune response. While the former contributes to parasite replication, the latter is crucial for its control. In the present review, we collected study results that associate arginase expression in patients and in experimental models with disease susceptibility/chronicity and show some proposed mechanisms that explain the role of arginase in maintaining Leishmania infection, including polyamine and thiol synthesis, tissue-resident macrophage (TRM) proliferation and activation and T-cell suppression and exhaustion.

Keywords: L-arginine; T-lymphocytes; arginase; chronic infection; leishmaniasis; macrophages; neutrophils.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arginase / metabolism*
  • CD8-Positive T-Lymphocytes / immunology
  • Humans
  • Immunity, Innate / immunology
  • Leishmania / immunology*
  • Leishmaniasis / immunology*
  • Leishmaniasis / parasitology
  • Macrophages / immunology*
  • Neutrophils / immunology
  • Nitric Oxide Synthase Type II / metabolism*
  • Th1 Cells / immunology
  • Th2 Cells / immunology

Substances

  • NOS2 protein, human
  • Nitric Oxide Synthase Type II
  • Arginase