Cargando…

IL-10 and TGF-β Induced Arginase Expression Contributes to Deficient Nitric Oxide Response in Human Visceral Leishmaniasis

Nitric oxide (NO) is an anti-microbial effector of the innate immune system which plays major role in non-specific killing of various pathogens including protozoan parasites. However, due to subversion of the host’s immune processes by pathogens, suboptimal production of NO is frequently found in ma...

Descripción completa

Detalles Bibliográficos
Autores principales: Kupani, Manu, Sharma, Smriti, Pandey, Rajeev Kumar, Kumar, Rajiv, Sundar, Shyam, Mehrotra, Sanjana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930829/
https://www.ncbi.nlm.nih.gov/pubmed/33680983
http://dx.doi.org/10.3389/fcimb.2020.614165
_version_ 1783660164234084352
author Kupani, Manu
Sharma, Smriti
Pandey, Rajeev Kumar
Kumar, Rajiv
Sundar, Shyam
Mehrotra, Sanjana
author_facet Kupani, Manu
Sharma, Smriti
Pandey, Rajeev Kumar
Kumar, Rajiv
Sundar, Shyam
Mehrotra, Sanjana
author_sort Kupani, Manu
collection PubMed
description Nitric oxide (NO) is an anti-microbial effector of the innate immune system which plays major role in non-specific killing of various pathogens including protozoan parasites. However, due to subversion of the host’s immune processes by pathogens, suboptimal production of NO is frequently found in many infection models. Previous studies have shown suppressed NO production during Leishmania donovani infection, the causative agent of visceral leishmaniasis (VL). Availability of L-Arginine, a semi-essential amino acid is required for inducible nitric oxide synthase (iNOS) mediated NO production. However, arginase is another enzyme, which if expressed concomitantly, may strongly compete for L-Arginine, and suppress NO production by iNOS. In the present study, plasma nitrite and arginase levels were measured in VL patients before and after successful drug treatment, endemic and non-endemic healthy donors. We observed significantly lower NO levels in the plasma of VL patients as compared to endemic controls, which improved significantly post-treatment. Significantly elevated arginase activity was also observed in the plasma of VL patients, which may be associated with NO deficiency. VL patients also showed significantly higher levels of IL-10 and TGF-β, which are known to regulate expression of arginase in various immune cells. In vitro studies with human peripheral blood mononuclear cells (PBMCs) further corroborated the role of IL-10 and TGF-β in arginase mediated suppression of NO production.
format Online
Article
Text
id pubmed-7930829
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-79308292021-03-05 IL-10 and TGF-β Induced Arginase Expression Contributes to Deficient Nitric Oxide Response in Human Visceral Leishmaniasis Kupani, Manu Sharma, Smriti Pandey, Rajeev Kumar Kumar, Rajiv Sundar, Shyam Mehrotra, Sanjana Front Cell Infect Microbiol Cellular and Infection Microbiology Nitric oxide (NO) is an anti-microbial effector of the innate immune system which plays major role in non-specific killing of various pathogens including protozoan parasites. However, due to subversion of the host’s immune processes by pathogens, suboptimal production of NO is frequently found in many infection models. Previous studies have shown suppressed NO production during Leishmania donovani infection, the causative agent of visceral leishmaniasis (VL). Availability of L-Arginine, a semi-essential amino acid is required for inducible nitric oxide synthase (iNOS) mediated NO production. However, arginase is another enzyme, which if expressed concomitantly, may strongly compete for L-Arginine, and suppress NO production by iNOS. In the present study, plasma nitrite and arginase levels were measured in VL patients before and after successful drug treatment, endemic and non-endemic healthy donors. We observed significantly lower NO levels in the plasma of VL patients as compared to endemic controls, which improved significantly post-treatment. Significantly elevated arginase activity was also observed in the plasma of VL patients, which may be associated with NO deficiency. VL patients also showed significantly higher levels of IL-10 and TGF-β, which are known to regulate expression of arginase in various immune cells. In vitro studies with human peripheral blood mononuclear cells (PBMCs) further corroborated the role of IL-10 and TGF-β in arginase mediated suppression of NO production. Frontiers Media S.A. 2021-02-18 /pmc/articles/PMC7930829/ /pubmed/33680983 http://dx.doi.org/10.3389/fcimb.2020.614165 Text en Copyright © 2021 Kupani, Sharma, Pandey, Kumar, Sundar and Mehrotra http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cellular and Infection Microbiology
Kupani, Manu
Sharma, Smriti
Pandey, Rajeev Kumar
Kumar, Rajiv
Sundar, Shyam
Mehrotra, Sanjana
IL-10 and TGF-β Induced Arginase Expression Contributes to Deficient Nitric Oxide Response in Human Visceral Leishmaniasis
title IL-10 and TGF-β Induced Arginase Expression Contributes to Deficient Nitric Oxide Response in Human Visceral Leishmaniasis
title_full IL-10 and TGF-β Induced Arginase Expression Contributes to Deficient Nitric Oxide Response in Human Visceral Leishmaniasis
title_fullStr IL-10 and TGF-β Induced Arginase Expression Contributes to Deficient Nitric Oxide Response in Human Visceral Leishmaniasis
title_full_unstemmed IL-10 and TGF-β Induced Arginase Expression Contributes to Deficient Nitric Oxide Response in Human Visceral Leishmaniasis
title_short IL-10 and TGF-β Induced Arginase Expression Contributes to Deficient Nitric Oxide Response in Human Visceral Leishmaniasis
title_sort il-10 and tgf-β induced arginase expression contributes to deficient nitric oxide response in human visceral leishmaniasis
topic Cellular and Infection Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7930829/
https://www.ncbi.nlm.nih.gov/pubmed/33680983
http://dx.doi.org/10.3389/fcimb.2020.614165
work_keys_str_mv AT kupanimanu il10andtgfbinducedarginaseexpressioncontributestodeficientnitricoxideresponseinhumanvisceralleishmaniasis
AT sharmasmriti il10andtgfbinducedarginaseexpressioncontributestodeficientnitricoxideresponseinhumanvisceralleishmaniasis
AT pandeyrajeevkumar il10andtgfbinducedarginaseexpressioncontributestodeficientnitricoxideresponseinhumanvisceralleishmaniasis
AT kumarrajiv il10andtgfbinducedarginaseexpressioncontributestodeficientnitricoxideresponseinhumanvisceralleishmaniasis
AT sundarshyam il10andtgfbinducedarginaseexpressioncontributestodeficientnitricoxideresponseinhumanvisceralleishmaniasis
AT mehrotrasanjana il10andtgfbinducedarginaseexpressioncontributestodeficientnitricoxideresponseinhumanvisceralleishmaniasis