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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Frontiers Media S.A.
2024-01-01
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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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