Leishmania guyanensis suppressed inducible nitric oxide synthase provoked by its viral endosymbiont.

Details

Serval ID
serval:BIB_A72D8B03FFC4
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Leishmania guyanensis suppressed inducible nitric oxide synthase provoked by its viral endosymbiont.
Journal
Frontiers in cellular and infection microbiology
Author(s)
Kopelyanskiy D., Desponds C., Prevel F., Rossi M., Migliorini R., Snäkä T., Eren R.O., Claudinot S., Lye L.F., Pasparakis M., Beverley S.M., Fasel N.
ISSN
2235-2988 (Electronic)
ISSN-L
2235-2988
Publication state
Published
Issued date
2022
Peer-reviewed
Oui
Volume
12
Pages
944819
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
Inducible nitric oxide synthase (iNOS) is essential to the production of nitric oxide (NO), an efficient effector molecule against intracellular human pathogens such as Leishmania protozoan parasites. Some strains of Leishmania are known to bear a viral endosymbiont termed Leishmania RNA virus 1 (LRV1). Recognition of LRV1 by the innate immune sensor Toll-like receptor-3 (TLR3) leads to conditions worsening the disease severity in mice. This process is governed by type I interferon (type I IFNs) arising downstream of TLR3 stimulation and favoring the formation of secondary metastatic lesions. The formation of these lesions is mediated by the inflammatory cytokine IL-17A and occurs in the absence, or low level of, protective cytokine IFN-γ. Here, we described that the presence of LRV1 led to the initial expression of iNOS and low production of NO that failed to control infection. We subsequently showed that LRV1-triggered type I IFN was essential but insufficient to induce robust iNOS induction, which requires strong activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). Leishmania guyanensis carrying LRV1 (LgyLRV1+) parasites mitigated strong iNOS production by limiting NF-kB activation via the induction of tumor necrosis factor-alpha-induced protein 3 (TNFAIP3), also known as A20. Moreover, our data suggested that production of LRV1-induced iNOS could be correlated with parasite dissemination and metastasis via elevated secretion of IL-17A in the draining lymph nodes. Our findings support an additional strategy by which LRV1-bearing Leishmania guyanensis evaded killing by nitric oxide and suggest that low levels of LRV1-induced NO might contribute to parasite metastasis.
Keywords
Animals, Cytokines, Humans, Interleukin-17, Leishmania, Leishmania guyanensis/virology, Leishmaniavirus, Mice, NF-kappa B, Nitric Oxide, Nitric Oxide Synthase Type II/metabolism, Toll-Like Receptor 3, IL-17A, Leishmania RNA virus 1 (LRV1), inducible nitric oxide synthase (iNOS), metastasis, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB), tumor necrosis factor-alpha-induced protein 3 (A20), type I Interferons
Pubmed
Web of science
Open Access
Yes
Create date
05/09/2022 9:20
Last modification date
22/09/2022 6:39
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