Innate resistance to Leishmania amazonensis Infection in rat is dependent on NOS2

Chen, Y-F; Yu, S-F; Wu, C-Y; Wu, N; Shen, J; Shen, J; Gao, J-M; Wen, Y-Z; Hide, G; Lai, D-H; Lun, Z-R

doi:10.3389/fmicb.2021.733286

Innate resistance to Leishmania amazonensis Infection in rat is dependent on NOS2

Chen, Y-F; Yu, S-F; Wu, C-Y; Wu, N; Shen, J; Shen, J; Gao, J-M; Wen, Y-Z; Hide, G; Lai, D-H; Lun, Z-R

Authors

Y-F Chen

S-F Yu

C-Y Wu

N Wu

J Shen

J-M Gao

Y-Z Wen

Prof Geoff Hide G.Hide@salford.ac.uk
Professor

D-H Lai

Z-R Lun

Contributors

E Von Stebut
Editor

MN Sotto
Other

JLM Wanderley
Other

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 Leishmania 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 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 L. amazonensis infection. Rats deficient in NOS2 are susceptible to L. amazonensis infection even though their immune response to infection is still strong. Moreover, adoptive transfer of NOS2 competent macrophages into Nos2−/− 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 Leishmania. These data highlight that macrophages from different hosts possess distinctive properties and produce different outcomes in innate immunity to Leishmania infections.

Journal Article Type	Article
Acceptance Date	Sep 27, 2021
Online Publication Date	Oct 29, 2021
Publication Date	Oct 29, 2021
Deposit Date	Nov 12, 2021
Publicly Available Date	Nov 12, 2021
Journal	Frontiers in Microbiology
Electronic ISSN	1664-302X
Publisher	Frontiers Media
Volume	12
Pages	733286
DOI	https://doi.org/10.3389/fmicb.2021.733286
Publisher URL	https://doi.org/10.3389/fmicb.2021.733286
Related Public URLs	http://www.frontiersin.org/journals/310
Additional Information	Additional Information : From Frontiers via Jisc Publications Router Licence for this article: http://creativecommons.org/licenses/by/4.0/ Journal IDs: eissn 1664-302X History: published_online 29-10-2021; accepted 27-09-2021; submitted 30-06-2021; collection 2021 Funders : National Natural Science Foundation of China;Natural Science Foundation of Guangdong Province Projects : 31720103918 and 31672276 Grant Number: 31720103918 and 31672276 Grant Number: 2018A030313187