Myeloid Cell Crosstalk Regulates the Efficacy of the DNA/ALVAC/gp120 HIV Vaccine Candidate
Vaccination with DNA-SIV + ALVAC-SIV + gp120 alum results in inflammasome activation, high levels of IL-1β production, emergency myelopoiesis, and the egress of CXCR4+ CD14+ pre-monocytes from bone marrow. Previously we have shown that this vaccine-induced innate monocyte memory is associated with d...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-05-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.01072/full |
| _version_ | 1811303454180638720 |
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| author | Monica Vaccari Slim Fourati Dallas R. Brown Isabela Silva de Castro Massimiliano Bissa Luca Schifanella Melvin N. Doster Kathryn E. Foulds Mario Roederer Richard A. Koup Yongjun Sui Jay A. Berzofsky Rafick-Pierre Sekaly Genoveffa Franchini |
| author_facet | Monica Vaccari Slim Fourati Dallas R. Brown Isabela Silva de Castro Massimiliano Bissa Luca Schifanella Melvin N. Doster Kathryn E. Foulds Mario Roederer Richard A. Koup Yongjun Sui Jay A. Berzofsky Rafick-Pierre Sekaly Genoveffa Franchini |
| author_sort | Monica Vaccari |
| collection | DOAJ |
| description | Vaccination with DNA-SIV + ALVAC-SIV + gp120 alum results in inflammasome activation, high levels of IL-1β production, emergency myelopoiesis, and the egress of CXCR4+ CD14+ pre-monocytes from bone marrow. Previously we have shown that this vaccine-induced innate monocyte memory is associated with decreased risk of SIVmac251 acquisition. Because IL-1β also promotes the propagation of monocyte-derived suppressor (M-MDSC)-like cells, here we extended our analysis to this negative regulator subset, characterizing its levels and functions in macaques. Interestingly, we found that DNA prime engages M-MDSC-like cells and their levels are positively associated with the frequency of CD14+ classical monocytes, and negatively with the levels of CD16+ monocytes, correlates of decreased and increased risk of SIV acquisition, respectively. Accordingly, M-MDSC frequency, arginase activity, and NO were all associated with decrease of CD8 T cells responses and worse vaccination outcome. DNA vaccination thus induces innate immunity by engaging three subsets of myeloid cells, M-MDSCs, CD14+ innate monocyte memory, and CD16+ monocytes all playing different role in protection. The full characterization of the immunological space created by myeloid cell crosstalk will likely provide clues to improve the efficacy of HIV vaccine candidates. |
| first_indexed | 2024-04-13T07:48:24Z |
| format | Article |
| id | doaj.art-b456d75223ed40b68fd3299cd3e0c444 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-04-13T07:48:24Z |
| publishDate | 2019-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-b456d75223ed40b68fd3299cd3e0c4442022-12-22T02:55:38ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-05-011010.3389/fimmu.2019.01072458528Myeloid Cell Crosstalk Regulates the Efficacy of the DNA/ALVAC/gp120 HIV Vaccine CandidateMonica Vaccari0Slim Fourati1Dallas R. Brown2Isabela Silva de Castro3Massimiliano Bissa4Luca Schifanella5Melvin N. Doster6Kathryn E. Foulds7Mario Roederer8Richard A. Koup9Yongjun Sui10Jay A. Berzofsky11Rafick-Pierre Sekaly12Genoveffa Franchini13Animal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United StatesDepartment of Pathology, Case Western Reserve University, Cleveland, OH, United StatesAnimal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United StatesAnimal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United StatesAnimal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United StatesAnimal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United StatesAnimal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United StatesVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesVaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, United StatesVaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United StatesVaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United StatesDepartment of Pathology, Case Western Reserve University, Cleveland, OH, United StatesAnimal Models and Retroviral Vaccines Section, Vaccine Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, United StatesVaccination with DNA-SIV + ALVAC-SIV + gp120 alum results in inflammasome activation, high levels of IL-1β production, emergency myelopoiesis, and the egress of CXCR4+ CD14+ pre-monocytes from bone marrow. Previously we have shown that this vaccine-induced innate monocyte memory is associated with decreased risk of SIVmac251 acquisition. Because IL-1β also promotes the propagation of monocyte-derived suppressor (M-MDSC)-like cells, here we extended our analysis to this negative regulator subset, characterizing its levels and functions in macaques. Interestingly, we found that DNA prime engages M-MDSC-like cells and their levels are positively associated with the frequency of CD14+ classical monocytes, and negatively with the levels of CD16+ monocytes, correlates of decreased and increased risk of SIV acquisition, respectively. Accordingly, M-MDSC frequency, arginase activity, and NO were all associated with decrease of CD8 T cells responses and worse vaccination outcome. DNA vaccination thus induces innate immunity by engaging three subsets of myeloid cells, M-MDSCs, CD14+ innate monocyte memory, and CD16+ monocytes all playing different role in protection. The full characterization of the immunological space created by myeloid cell crosstalk will likely provide clues to improve the efficacy of HIV vaccine candidates.https://www.frontiersin.org/article/10.3389/fimmu.2019.01072/fullMDSCtrained immunitymyeloid cellsHIV/SIVvaccine |
| spellingShingle | Monica Vaccari Slim Fourati Dallas R. Brown Isabela Silva de Castro Massimiliano Bissa Luca Schifanella Melvin N. Doster Kathryn E. Foulds Mario Roederer Richard A. Koup Yongjun Sui Jay A. Berzofsky Rafick-Pierre Sekaly Genoveffa Franchini Myeloid Cell Crosstalk Regulates the Efficacy of the DNA/ALVAC/gp120 HIV Vaccine Candidate Frontiers in Immunology MDSC trained immunity myeloid cells HIV/SIV vaccine |
| title | Myeloid Cell Crosstalk Regulates the Efficacy of the DNA/ALVAC/gp120 HIV Vaccine Candidate |
| title_full | Myeloid Cell Crosstalk Regulates the Efficacy of the DNA/ALVAC/gp120 HIV Vaccine Candidate |
| title_fullStr | Myeloid Cell Crosstalk Regulates the Efficacy of the DNA/ALVAC/gp120 HIV Vaccine Candidate |
| title_full_unstemmed | Myeloid Cell Crosstalk Regulates the Efficacy of the DNA/ALVAC/gp120 HIV Vaccine Candidate |
| title_short | Myeloid Cell Crosstalk Regulates the Efficacy of the DNA/ALVAC/gp120 HIV Vaccine Candidate |
| title_sort | myeloid cell crosstalk regulates the efficacy of the dna alvac gp120 hiv vaccine candidate |
| topic | MDSC trained immunity myeloid cells HIV/SIV vaccine |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.01072/full |
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