The role of TLR-4 in the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum

Introduction: An earlier constructed recombinant BCG expressing the MSP-1C of Plasmodium falciparum, induced inflammatory responses leading to significant production of nitric oxide (NO) alongside higher expression of the enzyme inducible nitric oxide synthase (iNOS) and significant production of t...

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Main Authors: Muhammad Adamu Abbas, Rapeah Suppian
Format: Article
Language:English
Published: The Journal of Infection in Developing Countries 2019-11-01
Series:Journal of Infection in Developing Countries
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Online Access:https://jidc.org/index.php/journal/article/view/11331
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author Muhammad Adamu Abbas
Rapeah Suppian
author_facet Muhammad Adamu Abbas
Rapeah Suppian
author_sort Muhammad Adamu Abbas
collection DOAJ
description Introduction: An earlier constructed recombinant BCG expressing the MSP-1C of Plasmodium falciparum, induced inflammatory responses leading to significant production of nitric oxide (NO) alongside higher expression of the enzyme inducible nitric oxide synthase (iNOS) and significant production of the regulatory cytokine, IL-10, indicating significant immunomodulatory effects of the construct. The mechanism of these responses had not been established but is thought to involve toll-like receptor 4 (TLR-4). Methodology: The present study was carried out to determine the role of TLR-4 on eliciting the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum leading to the production of NO and IL-10, as well as the expression of iNOS. Six groups of mice (n = 6 per group) were immunised thrice, three weeks apart with intraperitoneal phosphate buffered saline T80 (PBS-T80), BCG or rBCG in the presence or absence of a TLR-4 inhibitor; TAK-242, given one hour prior to each immunisation. Peritoneal macrophages were harvested from the mice and cultured for the determination of NO, iNOS and IL-10 via Griess assay, ELISA and Western blot respectively. Results: The results showed significant inhibition of the production of NO and IL-10 and the expression of iNOS in all groups of mice in the presence of TAK-242. Conclusions: These results presented evidence of the role of TLR-4/rBCG attachment mechanism in modulating the production of NO and IL-10 and the expression of iNOS in response to our rBCG-based malaria vaccine candidate expressing MSP-1C of P. falciparum.
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spelling doaj-art-19b555d6ae534f8c8cf4016ec99539f22025-08-20T03:52:41ZengThe Journal of Infection in Developing CountriesJournal of Infection in Developing Countries1972-26802019-11-01131110.3855/jidc.11331The role of TLR-4 in the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparumMuhammad Adamu Abbas0Rapeah Suppian1School of Health Sciences, Health Campus, Universiti Sains Malaysia, Kelantan, MalaysiaSchool of Health Sciences, Health Campus, Universiti Sains Malaysia, Kelantan, Malaysia Introduction: An earlier constructed recombinant BCG expressing the MSP-1C of Plasmodium falciparum, induced inflammatory responses leading to significant production of nitric oxide (NO) alongside higher expression of the enzyme inducible nitric oxide synthase (iNOS) and significant production of the regulatory cytokine, IL-10, indicating significant immunomodulatory effects of the construct. The mechanism of these responses had not been established but is thought to involve toll-like receptor 4 (TLR-4). Methodology: The present study was carried out to determine the role of TLR-4 on eliciting the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum leading to the production of NO and IL-10, as well as the expression of iNOS. Six groups of mice (n = 6 per group) were immunised thrice, three weeks apart with intraperitoneal phosphate buffered saline T80 (PBS-T80), BCG or rBCG in the presence or absence of a TLR-4 inhibitor; TAK-242, given one hour prior to each immunisation. Peritoneal macrophages were harvested from the mice and cultured for the determination of NO, iNOS and IL-10 via Griess assay, ELISA and Western blot respectively. Results: The results showed significant inhibition of the production of NO and IL-10 and the expression of iNOS in all groups of mice in the presence of TAK-242. Conclusions: These results presented evidence of the role of TLR-4/rBCG attachment mechanism in modulating the production of NO and IL-10 and the expression of iNOS in response to our rBCG-based malaria vaccine candidate expressing MSP-1C of P. falciparum. https://jidc.org/index.php/journal/article/view/11331ImmunityMalariaMSP-1rBCGTLR-4Vaccine
spellingShingle Muhammad Adamu Abbas
Rapeah Suppian
The role of TLR-4 in the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum
Journal of Infection in Developing Countries
Immunity
Malaria
MSP-1
rBCG
TLR-4
Vaccine
title The role of TLR-4 in the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum
title_full The role of TLR-4 in the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum
title_fullStr The role of TLR-4 in the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum
title_full_unstemmed The role of TLR-4 in the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum
title_short The role of TLR-4 in the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum
title_sort role of tlr 4 in the immunomodulatory effects of recombinant bcg expressing msp 1c of plasmodium falciparum
topic Immunity
Malaria
MSP-1
rBCG
TLR-4
Vaccine
url https://jidc.org/index.php/journal/article/view/11331
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