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 ORCID: https://orcid.org/0000-0002-3608-0175, Lai, D-H and Lun, Z-R 2021, 'Innate resistance to Leishmania amazonensis Infection in rat is dependent on NOS2' , Frontiers in Microbiology, 12 , p. 733286.

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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.

Item Type: Article
Contributors: Von Stebut, E (Editor), Sotto, MN (Reviewer) and Wanderley, JLM (Reviewer)
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
Schools: Schools > School of Environment and Life Sciences
Journal or Publication Title: Frontiers in Microbiology
Publisher: Frontiers Media S.A.
ISSN: 1664-302X
Related URLs:
Funders: National Natural Science Foundation of China, Natural Science Foundation of Guangdong Province
SWORD Depositor: Publications Router
Depositing User: Publications Router
Date Deposited: 12 Nov 2021 09:43
Last Modified: 12 Nov 2021 09:45
URI: http://usir.salford.ac.uk/id/eprint/62347

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