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Innate Resistance to Leishmania amazonensis Infection in Rat Is Dependent on NOS2

Yun-Fu Chen1, Si-Fei Yu2, Chang-You Wu2

  • 1Guangdong Provincial Key Laboratory of Aquatic Economic Animals, Key Laboratory of Gene Engineering of the Ministry of Education, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China.

Frontiers in Microbiology
|November 15, 2021
PubMed

Insights

Rats resist Leishmania amazonensis infection due to a specific nitric oxide synthase pathway (NOS2). Macrophages lacking NOS2 become susceptible, highlighting NOS2

Area of Science:

  • Immunology
  • Infectious Diseases
  • Parasitology

Background:

  • Leishmania infection presents diverse clinical outcomes influenced by host and parasite factors.
  • Mice show variable resistance to Leishmania major but high susceptibility to Leishmania amazonensis.
  • Rats exhibit strong resistance to Leishmania amazonensis, with underlying mechanisms previously unknown.

Purpose of the Study:

  • To investigate the role of inducible nitric oxide synthase (NOS2) in rat resistance to Leishmania amazonensis infection.
  • To elucidate the mechanisms behind rat innate immunity against Leishmania.

Main Methods:

  • Utilized a NOS2 gene knockout rat model (Nos2-/- rat).
  • Assessed susceptibility to Leishmania amazonensis infection in wild-type and Nos2-/- rats.
  • Performed adoptive transfer of NOS2-competent macrophages into Nos2-/- rats.

Main Results:

  • Diversion toward the NOS2 pathway is critical for rat resistance against Leishmania amazonensis.
  • Nos2-/- rats are susceptible to Leishmania amazonensis infection despite a robust immune response.
  • Adoptive transfer of NOS2-competent macrophages significantly reduced disease progression and parasite burden in Nos2-/- rats.

Conclusions:

  • Distinct L-arginine metabolism in rat macrophages, leading to NOS2 activation, forms the basis of strong innate resistance to Leishmania.
  • Macrophages possess unique properties across different hosts, influencing innate immune responses and disease outcomes in Leishmania infections.
Keywords:
Leishmania (L.) amazonensisadoptive transferiNOS knock outnitric oxiderat peritoneal macrophages

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