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=12

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=<p><italic>Leishmania</italic> 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 <italic>Leishmania major</italic> but are highly susceptible to <italic>Leishmania amazonensis</italic> infection. However, rats are highly resistant to <italic>L. amazonensis</italic> infection due to unknown mechanisms. We use the inducible nitric oxide synthase (<italic>Nos2)</italic> gene knockout rat model (<italic>Nos2</italic><sup>−/−</sup> rat) to investigate the role of NOS2 against leishmania infection in rats. Our results demonstrated that diversion toward the NOS2 pathway is the key factor explaining the resistance of rats against <italic>L. amazonensis</italic> infection. Rats deficient in NOS2 are susceptible to <italic>L. amazonensis</italic> infection even though their immune response to infection is still strong. Moreover, adoptive transfer of NOS2 competent macrophages into <italic>Nos2</italic><sup>−/−</sup> rats significantly reduced disease development and parasite load. Thus, we conclude that the distinct L-arginine metabolism, observed in rat macrophages, is the basis of the strong innate resistance to <italic>Leishmania</italic>. These data highlight that macrophages from different hosts possess distinctive properties and produce different outcomes in innate immunity to <italic>Leishmania</italic> infections.</p>