Infection order outweighs the role of CD4+ T cells in tertiary flavivirus exposure
Summary: The link between CD4+ T and B cells during immune responses to DENV and ZIKV and their roles in cross-protection during heterologous infection is an active area of research. Here we used CD4+ lymphocyte depletions to dissect the impact of cellular immunity on humoral responses during a tert...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-08-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004222010367 |
| _version_ | 1811345287705264128 |
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| author | Nicole Marzan-Rivera Crisanta Serrano-Collazo Lorna Cruz Petraleigh Pantoja Alexandra Ortiz-Rosa Teresa Arana Melween I. Martinez Armando G. Burgos Chiara Roman Loyda B. Mendez Elizabeth Geerling Amelia K. Pinto James D. Brien Carlos A. Sariol |
| author_facet | Nicole Marzan-Rivera Crisanta Serrano-Collazo Lorna Cruz Petraleigh Pantoja Alexandra Ortiz-Rosa Teresa Arana Melween I. Martinez Armando G. Burgos Chiara Roman Loyda B. Mendez Elizabeth Geerling Amelia K. Pinto James D. Brien Carlos A. Sariol |
| author_sort | Nicole Marzan-Rivera |
| collection | DOAJ |
| description | Summary: The link between CD4+ T and B cells during immune responses to DENV and ZIKV and their roles in cross-protection during heterologous infection is an active area of research. Here we used CD4+ lymphocyte depletions to dissect the impact of cellular immunity on humoral responses during a tertiary flavivirus infection in macaques. We show that CD4+ depletion in DENV/ZIKV-primed animals followed by DENV resulted in dysregulated adaptive immune responses. We show a delay in DENV-specific IgM/IgG antibody titers and binding and neutralization in the DENV/ZIKV-primed CD4-depleted animals but not in ZIKV/DENV-primed CD4-depleted animals. This study confirms the critical role of CD4+ cells in priming an early effective humoral response during sequential flavivirus infections. Our work here suggests that the order of flavivirus exposure affects the outcome of a tertiary infection. Our findings have implications for understanding the complex flavivirus immune responses and for the development of effective flavivirus vaccines. |
| first_indexed | 2024-04-13T20:00:53Z |
| format | Article |
| id | doaj.art-106a553bcf544ebe8c208514146b652c |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-13T20:00:53Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-106a553bcf544ebe8c208514146b652c2022-12-22T02:32:12ZengElsevieriScience2589-00422022-08-01258104764Infection order outweighs the role of CD4+ T cells in tertiary flavivirus exposureNicole Marzan-Rivera0Crisanta Serrano-Collazo1Lorna Cruz2Petraleigh Pantoja3Alexandra Ortiz-Rosa4Teresa Arana5Melween I. Martinez6Armando G. Burgos7Chiara Roman8Loyda B. Mendez9Elizabeth Geerling10Amelia K. Pinto11James D. Brien12Carlos A. Sariol13Department of Microbiology and Medical Zoology, University of Puerto Rico-Medical Sciences Campus, San Juan, PR 00935, USAUnit of Comparative Medicine, University of Puerto Rico-Medical Sciences Campus, San Juan, PR 00935, USADepartment of Microbiology and Medical Zoology, University of Puerto Rico-Medical Sciences Campus, San Juan, PR 00935, USA; Unit of Comparative Medicine, University of Puerto Rico-Medical Sciences Campus, San Juan, PR 00935, USAUnit of Comparative Medicine, University of Puerto Rico-Medical Sciences Campus, San Juan, PR 00935, USADepartment of Biology, University of Puerto Rico Rio Piedras Campus, San Juan, PR 00931, USADepartment of Microbiology and Medical Zoology, University of Puerto Rico-Medical Sciences Campus, San Juan, PR 00935, USA; Unit of Comparative Medicine, University of Puerto Rico-Medical Sciences Campus, San Juan, PR 00935, USAUnit of Comparative Medicine, University of Puerto Rico-Medical Sciences Campus, San Juan, PR 00935, USA; Caribbean Primate Research Center, School of Medicine, University of Puerto Rico-Medical Sciences Campus, Toa Baja, PR 00952, USAUnit of Comparative Medicine, University of Puerto Rico-Medical Sciences Campus, San Juan, PR 00935, USA; Caribbean Primate Research Center, School of Medicine, University of Puerto Rico-Medical Sciences Campus, Toa Baja, PR 00952, USAUnit of Comparative Medicine, University of Puerto Rico-Medical Sciences Campus, San Juan, PR 00935, USADepartment of Science & Technology, Universidad Ana G. Mendez, Recinto de Carolina, Carolina, PR 00985, USADepartment of Molecular Microbiology and Immunology, Saint Louis University, St Louis, MO 631204, USADepartment of Molecular Microbiology and Immunology, Saint Louis University, St Louis, MO 631204, USADepartment of Molecular Microbiology and Immunology, Saint Louis University, St Louis, MO 631204, USADepartment of Microbiology and Medical Zoology, University of Puerto Rico-Medical Sciences Campus, San Juan, PR 00935, USA; Unit of Comparative Medicine, University of Puerto Rico-Medical Sciences Campus, San Juan, PR 00935, USA; Department of Biology, University of Puerto Rico Rio Piedras Campus, San Juan, PR 00931, USA; Department of Internal Medicine, University of Puerto Rico-Medical Sciences Campus, San Juan, PR 00935, USA; Corresponding authorSummary: The link between CD4+ T and B cells during immune responses to DENV and ZIKV and their roles in cross-protection during heterologous infection is an active area of research. Here we used CD4+ lymphocyte depletions to dissect the impact of cellular immunity on humoral responses during a tertiary flavivirus infection in macaques. We show that CD4+ depletion in DENV/ZIKV-primed animals followed by DENV resulted in dysregulated adaptive immune responses. We show a delay in DENV-specific IgM/IgG antibody titers and binding and neutralization in the DENV/ZIKV-primed CD4-depleted animals but not in ZIKV/DENV-primed CD4-depleted animals. This study confirms the critical role of CD4+ cells in priming an early effective humoral response during sequential flavivirus infections. Our work here suggests that the order of flavivirus exposure affects the outcome of a tertiary infection. Our findings have implications for understanding the complex flavivirus immune responses and for the development of effective flavivirus vaccines.http://www.sciencedirect.com/science/article/pii/S2589004222010367ImmunologyVirology |
| spellingShingle | Nicole Marzan-Rivera Crisanta Serrano-Collazo Lorna Cruz Petraleigh Pantoja Alexandra Ortiz-Rosa Teresa Arana Melween I. Martinez Armando G. Burgos Chiara Roman Loyda B. Mendez Elizabeth Geerling Amelia K. Pinto James D. Brien Carlos A. Sariol Infection order outweighs the role of CD4+ T cells in tertiary flavivirus exposure iScience Immunology Virology |
| title | Infection order outweighs the role of CD4+ T cells in tertiary flavivirus exposure |
| title_full | Infection order outweighs the role of CD4+ T cells in tertiary flavivirus exposure |
| title_fullStr | Infection order outweighs the role of CD4+ T cells in tertiary flavivirus exposure |
| title_full_unstemmed | Infection order outweighs the role of CD4+ T cells in tertiary flavivirus exposure |
| title_short | Infection order outweighs the role of CD4+ T cells in tertiary flavivirus exposure |
| title_sort | infection order outweighs the role of cd4 t cells in tertiary flavivirus exposure |
| topic | Immunology Virology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004222010367 |
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