Immunomodulatory Effects of Recombinant <i>Mycobacterium smegmatis</i> Expressing Antigen-85B Epitopes in Infected J774A.1 Murine Macrophages
Tuberculosis (TB) causes more than 1.5 million deaths each year, remaining a significant global health problem. <i>Mycobacterium smegmatis</i> (<i>M. smegmatis</i>) and <i>Mycobacterium tuberculosis</i> (<i>M. tuberculosis</i>) share features, which su...
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doaj-f2c75ad7afff4eaba6b873bb9ce7cde92020-11-30T00:02:09ZengMDPI AGPathogens2076-08172020-11-0191000100010.3390/pathogens9121000Immunomodulatory Effects of Recombinant <i>Mycobacterium smegmatis</i> Expressing Antigen-85B Epitopes in Infected J774A.1 Murine MacrophagesNur-Ayuni Kadir0Armando Acosta1Maria E. Sarmiento2Mohd-Nor Norazmi3School of Biomedicine, Faculty of Health Sciences, Universiti Sultan Zainal Abidin, Kuala Nerus 21300, Terengganu, MalaysiaSchool of Health Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, MalaysiaSchool of Health Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, MalaysiaSchool of Health Sciences, Universiti Sains Malaysia, Kubang Kerian 16150, Kelantan, MalaysiaTuberculosis (TB) causes more than 1.5 million deaths each year, remaining a significant global health problem. <i>Mycobacterium smegmatis</i> (<i>M. smegmatis</i>) and <i>Mycobacterium tuberculosis</i> (<i>M. tuberculosis</i>) share features, which support the use of the former use in new generation TB vaccine development. In a previous study, the specific humoral and cellular immunogenicity of a recombinant <i>M. smegmatis</i> strain expressing epitopes from <i>M. tuberculosis</i> Ag85B protein (rMs064), was demonstrated in mice. In the current study, the immunomodulatory capacity of rMs064 was determined in a J774A.1 murine macrophage cell line. To determine the immunomodulatory effect of rMs064 in J774A.1 macrophages, the expression of inducible nitric oxide synthase (iNOS) and production of nitric oxide (NO) was evaluated. The expression of activation surface markers (MHC-II, CD40, CD80 and CD86) and the production of cytokines (IL-1β, TNF-α, IL-12p70 and IL-6) was also determined in rMs064 infected J774A.1 macrophages. Our findings showed the ability of rMs064 to induce substantial increases in macrophage activation markers expression; MHC class II and CD40, compared with <i>M. smegmatis t</i>ransformed with the empty vector (rMs012) and uninfected cells. rMs064 induced significant increases in IL-12p70 compared to uninfected cells. The expression of iNOS and CD86, and the production of IL-1β, and TNF-α were increased in rMs064 and rMs012, compared to uninfected cells. rMs064 demonstrated its immunomodulatory ability by stimulating the innate immune response, which supports its further evaluation as a TB vaccine candidate.https://www.mdpi.com/2076-0817/9/12/1000tuberculosisBCGmycobacteria<i>M. tuberculosis</i><i>M. smegmatis</i>antigen-85B |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Nur-Ayuni Kadir Armando Acosta Maria E. Sarmiento Mohd-Nor Norazmi |
spellingShingle |
Nur-Ayuni Kadir Armando Acosta Maria E. Sarmiento Mohd-Nor Norazmi Immunomodulatory Effects of Recombinant <i>Mycobacterium smegmatis</i> Expressing Antigen-85B Epitopes in Infected J774A.1 Murine Macrophages Pathogens tuberculosis BCG mycobacteria <i>M. tuberculosis</i> <i>M. smegmatis</i> antigen-85B |
author_facet |
Nur-Ayuni Kadir Armando Acosta Maria E. Sarmiento Mohd-Nor Norazmi |
author_sort |
Nur-Ayuni Kadir |
title |
Immunomodulatory Effects of Recombinant <i>Mycobacterium smegmatis</i> Expressing Antigen-85B Epitopes in Infected J774A.1 Murine Macrophages |
title_short |
Immunomodulatory Effects of Recombinant <i>Mycobacterium smegmatis</i> Expressing Antigen-85B Epitopes in Infected J774A.1 Murine Macrophages |
title_full |
Immunomodulatory Effects of Recombinant <i>Mycobacterium smegmatis</i> Expressing Antigen-85B Epitopes in Infected J774A.1 Murine Macrophages |
title_fullStr |
Immunomodulatory Effects of Recombinant <i>Mycobacterium smegmatis</i> Expressing Antigen-85B Epitopes in Infected J774A.1 Murine Macrophages |
title_full_unstemmed |
Immunomodulatory Effects of Recombinant <i>Mycobacterium smegmatis</i> Expressing Antigen-85B Epitopes in Infected J774A.1 Murine Macrophages |
title_sort |
immunomodulatory effects of recombinant <i>mycobacterium smegmatis</i> expressing antigen-85b epitopes in infected j774a.1 murine macrophages |
publisher |
MDPI AG |
series |
Pathogens |
issn |
2076-0817 |
publishDate |
2020-11-01 |
description |
Tuberculosis (TB) causes more than 1.5 million deaths each year, remaining a significant global health problem. <i>Mycobacterium smegmatis</i> (<i>M. smegmatis</i>) and <i>Mycobacterium tuberculosis</i> (<i>M. tuberculosis</i>) share features, which support the use of the former use in new generation TB vaccine development. In a previous study, the specific humoral and cellular immunogenicity of a recombinant <i>M. smegmatis</i> strain expressing epitopes from <i>M. tuberculosis</i> Ag85B protein (rMs064), was demonstrated in mice. In the current study, the immunomodulatory capacity of rMs064 was determined in a J774A.1 murine macrophage cell line. To determine the immunomodulatory effect of rMs064 in J774A.1 macrophages, the expression of inducible nitric oxide synthase (iNOS) and production of nitric oxide (NO) was evaluated. The expression of activation surface markers (MHC-II, CD40, CD80 and CD86) and the production of cytokines (IL-1β, TNF-α, IL-12p70 and IL-6) was also determined in rMs064 infected J774A.1 macrophages. Our findings showed the ability of rMs064 to induce substantial increases in macrophage activation markers expression; MHC class II and CD40, compared with <i>M. smegmatis t</i>ransformed with the empty vector (rMs012) and uninfected cells. rMs064 induced significant increases in IL-12p70 compared to uninfected cells. The expression of iNOS and CD86, and the production of IL-1β, and TNF-α were increased in rMs064 and rMs012, compared to uninfected cells. rMs064 demonstrated its immunomodulatory ability by stimulating the innate immune response, which supports its further evaluation as a TB vaccine candidate. |
topic |
tuberculosis BCG mycobacteria <i>M. tuberculosis</i> <i>M. smegmatis</i> antigen-85B |
url |
https://www.mdpi.com/2076-0817/9/12/1000 |
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