Impaired macrophage and memory T-cell responses to Bacillus Calmette-Guerin nonpolar lipid extract

IntroductionThe attenuation of BCG has led to the loss of not only immunogenic proteins but also lipid antigens.MethodsThus, we compared the macrophage and T-cell responses to nonpolar lipid extracts harvested from BCG and Mycobacterium tuberculosis (Mtb) to better understand the role of BCG lipids...

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Main Authors: Alice Sarno, Avelina Leite, Carlos Augusto, Igor Muller, Luanna de Ângelis, Lilian Pimentel, Adriano Queiroz, Sergio Arruda
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-01-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1263352/full
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author Alice Sarno
Alice Sarno
Avelina Leite
Carlos Augusto
Igor Muller
Luanna de Ângelis
Lilian Pimentel
Adriano Queiroz
Sergio Arruda
Sergio Arruda
author_facet Alice Sarno
Alice Sarno
Avelina Leite
Carlos Augusto
Igor Muller
Luanna de Ângelis
Lilian Pimentel
Adriano Queiroz
Sergio Arruda
Sergio Arruda
author_sort Alice Sarno
collection DOAJ
description IntroductionThe attenuation of BCG has led to the loss of not only immunogenic proteins but also lipid antigens.MethodsThus, we compared the macrophage and T-cell responses to nonpolar lipid extracts harvested from BCG and Mycobacterium tuberculosis (Mtb) to better understand the role of BCG lipids in the already known diminished responses of the vaccine strain.ResultsRelative to Mtb, nonpolar lipid extract from BCG presented a reduced capacity to trigger the expression of the genes encoding TNF, IL-1b, IL-6 and IL-10 in RAW 264.7 macrophages. Immunophenotyping of PBMCs isolated from healthy individuals revealed that lipids from both BCG and Mtb were able to induce an increased frequency of CD4+ and CD8+ T cells, but only the lipid extract from Mtb enhanced the frequency of CD4-CD8-double-negative, γσ+, CD4+HLA-DR+, and γσ+HLA-DR+ T cells relative to the nonstimulated control. Interestingly, only the Mtb lipid extract was able to increase the frequency of CD4+ memory (CD45RO+) T cells, whereas the BCG lipid extract induced a diminished frequency of CD4+ central memory (CD45RO+CCR7-) T cells after 48 h of culture compared to Mtb.DiscussionThese findings show that the nonpolar lipids of the BCG bacilli presented diminished ability to trigger both proinflammatory and memory responses and suggest a potential use of Mtb lipids as adjuvants to increase the BCG vaccine efficacy.
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spelling doaj.art-2cfea17b49284aefb9c89af70af3386a2024-01-11T04:55:14ZengFrontiers Media S.A.Frontiers in Immunology1664-32242024-01-011410.3389/fimmu.2023.12633521263352Impaired macrophage and memory T-cell responses to Bacillus Calmette-Guerin nonpolar lipid extractAlice Sarno0Alice Sarno1Avelina Leite2Carlos Augusto3Igor Muller4Luanna de Ângelis5Lilian Pimentel6Adriano Queiroz7Sergio Arruda8Sergio Arruda9Advanced Laboratory of Public Health, Gonçalo Moniz Institute, Fiocruz, Salvador, BrazilDepartment of Pathology and Forensic Medicine, Faculty of Medicine, Federal University of Bahia, Salvador, BrazilAdvanced Laboratory of Public Health, Gonçalo Moniz Institute, Fiocruz, Salvador, BrazilAdvanced Laboratory of Public Health, Gonçalo Moniz Institute, Fiocruz, Salvador, BrazilAdvanced Laboratory of Public Health, Gonçalo Moniz Institute, Fiocruz, Salvador, BrazilLaboratory of Immunoepidemiology, Aggeu Magalhães Institute, Fiocruz, Recife, BrazilLaboratory of Immunoepidemiology, Aggeu Magalhães Institute, Fiocruz, Recife, BrazilAdvanced Laboratory of Public Health, Gonçalo Moniz Institute, Fiocruz, Salvador, BrazilAdvanced Laboratory of Public Health, Gonçalo Moniz Institute, Fiocruz, Salvador, BrazilDepartment of Life Sciences, State University of Bahia, Salvador, BrazilIntroductionThe attenuation of BCG has led to the loss of not only immunogenic proteins but also lipid antigens.MethodsThus, we compared the macrophage and T-cell responses to nonpolar lipid extracts harvested from BCG and Mycobacterium tuberculosis (Mtb) to better understand the role of BCG lipids in the already known diminished responses of the vaccine strain.ResultsRelative to Mtb, nonpolar lipid extract from BCG presented a reduced capacity to trigger the expression of the genes encoding TNF, IL-1b, IL-6 and IL-10 in RAW 264.7 macrophages. Immunophenotyping of PBMCs isolated from healthy individuals revealed that lipids from both BCG and Mtb were able to induce an increased frequency of CD4+ and CD8+ T cells, but only the lipid extract from Mtb enhanced the frequency of CD4-CD8-double-negative, γσ+, CD4+HLA-DR+, and γσ+HLA-DR+ T cells relative to the nonstimulated control. Interestingly, only the Mtb lipid extract was able to increase the frequency of CD4+ memory (CD45RO+) T cells, whereas the BCG lipid extract induced a diminished frequency of CD4+ central memory (CD45RO+CCR7-) T cells after 48 h of culture compared to Mtb.DiscussionThese findings show that the nonpolar lipids of the BCG bacilli presented diminished ability to trigger both proinflammatory and memory responses and suggest a potential use of Mtb lipids as adjuvants to increase the BCG vaccine efficacy.https://www.frontiersin.org/articles/10.3389/fimmu.2023.1263352/fullBacillus Calmette-GuerinMycobacterium tuberculosisnonpolar lipid extractsmacrophage gene expressionmemory T-cell responses
spellingShingle Alice Sarno
Alice Sarno
Avelina Leite
Carlos Augusto
Igor Muller
Luanna de Ângelis
Lilian Pimentel
Adriano Queiroz
Sergio Arruda
Sergio Arruda
Impaired macrophage and memory T-cell responses to Bacillus Calmette-Guerin nonpolar lipid extract
Frontiers in Immunology
Bacillus Calmette-Guerin
Mycobacterium tuberculosis
nonpolar lipid extracts
macrophage gene expression
memory T-cell responses
title Impaired macrophage and memory T-cell responses to Bacillus Calmette-Guerin nonpolar lipid extract
title_full Impaired macrophage and memory T-cell responses to Bacillus Calmette-Guerin nonpolar lipid extract
title_fullStr Impaired macrophage and memory T-cell responses to Bacillus Calmette-Guerin nonpolar lipid extract
title_full_unstemmed Impaired macrophage and memory T-cell responses to Bacillus Calmette-Guerin nonpolar lipid extract
title_short Impaired macrophage and memory T-cell responses to Bacillus Calmette-Guerin nonpolar lipid extract
title_sort impaired macrophage and memory t cell responses to bacillus calmette guerin nonpolar lipid extract
topic Bacillus Calmette-Guerin
Mycobacterium tuberculosis
nonpolar lipid extracts
macrophage gene expression
memory T-cell responses
url https://www.frontiersin.org/articles/10.3389/fimmu.2023.1263352/full
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