AUTHOR=Chen Yun-Fu , Yu Si-Fei , Wu Chang-You , Wu Na , Shen Jia , Shen Juan , Gao Jiang-Mei , Wen Yan-Zi , Hide Geoff , Lai De-Hua , Lun Zhao-Rong 

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

JOURNAL=Frontiers in Microbiology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2021.733286

DOI=10.3389/fmicb.2021.733286

ISSN=1664-302X

ABSTRACT=Leishmania infection causes diverse clinical manifestations in humans. The disease outcome is complicated by the combination of many host and parasite factors. Inbred mouse strains vary in resistance to Leishmania major but are highly susceptible to L. amazonensis infection. However, rats are highly resistant to L. amazonensis infection due to unknown mechanisms. We use the inducible nitric oxide synthase (Nos2) gene knockout rat model (Nos2-/- rat) to investigate the role L-arginine metabolism against leishmania infection in rat. Our results demonstrated that diversion towards the NOS2 pathway is the key factor for the resistance of rats against L. amazonensis infection. Rats deficient in NOS2 are susceptible to L. amazonensis infection even though their immune responses against infection are still strong. Moreover, adoptive transfer of NOS2 competent macrophages into Nos2-/- rats significantly reduced disease development. Thus, we conclude that the distinct L-arginine metabolism in rat macrophages is the basis for the strong innate resistance to Leishmania. These data highlight that macrophages from different hosts possess distinctive properties and produce different outcomes in innate immunity against Leishmania infections.