Impaired Antibody-Independent Immune Response of B Cells in Patients With Acute Dengue Infection
Dengue is a mosquito-borne viral disease caused by dengue virus (DENV). The disease is endemic to more than 100 countries with 390 million dengue infections per year. Humoral immune responses during primary and secondary DENV infections are well-investigated. However, the impact of DENV infection on...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02500/full |
| _version_ | 1818258584222302208 |
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| author | Vinit Upasani Vinit Upasani Hoa Thi My Vo Sivlin Ung Sothy Heng Denis Laurent Rithy Choeung Veasna Duong Sopheak Sorn Sowath Ly Izabela A. Rodenhuis-Zybert Philippe Dussart Tineke Cantaert |
| author_facet | Vinit Upasani Vinit Upasani Hoa Thi My Vo Sivlin Ung Sothy Heng Denis Laurent Rithy Choeung Veasna Duong Sopheak Sorn Sowath Ly Izabela A. Rodenhuis-Zybert Philippe Dussart Tineke Cantaert |
| author_sort | Vinit Upasani |
| collection | DOAJ |
| description | Dengue is a mosquito-borne viral disease caused by dengue virus (DENV). The disease is endemic to more than 100 countries with 390 million dengue infections per year. Humoral immune responses during primary and secondary DENV infections are well-investigated. However, the impact of DENV infection on B cell subsets and their antibody-independent functions are not well-documented. Through this study, we aimed to define the distribution of B cell subsets in the acute phase of DENV infection and characterize the effect of DENV infection on B cell functions such as differentiation into memory and plasma cells and cytokine production. In our cohort of Cambodian children, we observed decreased percentages of CD24hiCD38hi B cells and CD27− naïve B cells within the CD19 population and increased percentages of CD27+CD38hiCD138+ plasma cells as early as 4 days post appearance of fever in patients with severe dengue compared to patients with mild disease. Lower percentages of CD19+CD24hiCD38hi B cells in DENV-infected patients were associated with decreased concentrations of soluble CD40L in patient plasma and decreased platelet counts in these patients. In addition, CD19+CD24hiCD38hi and CD19+CD27− B cells from DENV-infected patients did not produce IL-10 or TNF-α upon stimulation in vitro, suggesting their contribution to an altered immune response during DENV infection. In addition, CD19+CD27− naïve B cells isolated from dengue patients were refractory to TLR/anti-IgM stimulation in vitro, which correlated to the increased expression of inhibitory Fcγ receptors (FcγR) CD32 and LILRB1 on CD19+CD27− naïve B cells from DENV-infected patients. Collectively, our results indicate that a defective B cell response in dengue patients may contribute to the pathogenesis of dengue during the early phase of infection. |
| first_indexed | 2024-12-12T18:01:52Z |
| format | Article |
| id | doaj.art-2e671ce54aee4b57aed671f03a9bd209 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-12T18:01:52Z |
| publishDate | 2019-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-2e671ce54aee4b57aed671f03a9bd2092022-12-22T00:16:36ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-10-011010.3389/fimmu.2019.02500467035Impaired Antibody-Independent Immune Response of B Cells in Patients With Acute Dengue InfectionVinit Upasani0Vinit Upasani1Hoa Thi My Vo2Sivlin Ung3Sothy Heng4Denis Laurent5Rithy Choeung6Veasna Duong7Sopheak Sorn8Sowath Ly9Izabela A. Rodenhuis-Zybert10Philippe Dussart11Tineke Cantaert12Immunology Unit, Institut Pasteur du Cambodge, Institut Pasteur International Network, Phnom Penh, CambodiaDepartment of Medical Microbiology and Infection Prevention, University of Groningen and University Medical Center Groningen, Groningen, NetherlandsImmunology Unit, Institut Pasteur du Cambodge, Institut Pasteur International Network, Phnom Penh, CambodiaImmunology Unit, Institut Pasteur du Cambodge, Institut Pasteur International Network, Phnom Penh, CambodiaKantha Bopha Children Hospital, Phnom Penh, CambodiaKantha Bopha Children Hospital, Phnom Penh, CambodiaVirology Unit, Institut Pasteur du Cambodge, Institut Pasteur International Network, Phnom Penh, CambodiaVirology Unit, Institut Pasteur du Cambodge, Institut Pasteur International Network, Phnom Penh, CambodiaEpidemiology and Public Health Unit, Institut Pasteur du Cambodge, Institut Pasteur International Network, Phnom Penh, CambodiaEpidemiology and Public Health Unit, Institut Pasteur du Cambodge, Institut Pasteur International Network, Phnom Penh, CambodiaDepartment of Medical Microbiology and Infection Prevention, University of Groningen and University Medical Center Groningen, Groningen, NetherlandsVirology Unit, Institut Pasteur du Cambodge, Institut Pasteur International Network, Phnom Penh, CambodiaImmunology Unit, Institut Pasteur du Cambodge, Institut Pasteur International Network, Phnom Penh, CambodiaDengue is a mosquito-borne viral disease caused by dengue virus (DENV). The disease is endemic to more than 100 countries with 390 million dengue infections per year. Humoral immune responses during primary and secondary DENV infections are well-investigated. However, the impact of DENV infection on B cell subsets and their antibody-independent functions are not well-documented. Through this study, we aimed to define the distribution of B cell subsets in the acute phase of DENV infection and characterize the effect of DENV infection on B cell functions such as differentiation into memory and plasma cells and cytokine production. In our cohort of Cambodian children, we observed decreased percentages of CD24hiCD38hi B cells and CD27− naïve B cells within the CD19 population and increased percentages of CD27+CD38hiCD138+ plasma cells as early as 4 days post appearance of fever in patients with severe dengue compared to patients with mild disease. Lower percentages of CD19+CD24hiCD38hi B cells in DENV-infected patients were associated with decreased concentrations of soluble CD40L in patient plasma and decreased platelet counts in these patients. In addition, CD19+CD24hiCD38hi and CD19+CD27− B cells from DENV-infected patients did not produce IL-10 or TNF-α upon stimulation in vitro, suggesting their contribution to an altered immune response during DENV infection. In addition, CD19+CD27− naïve B cells isolated from dengue patients were refractory to TLR/anti-IgM stimulation in vitro, which correlated to the increased expression of inhibitory Fcγ receptors (FcγR) CD32 and LILRB1 on CD19+CD27− naïve B cells from DENV-infected patients. Collectively, our results indicate that a defective B cell response in dengue patients may contribute to the pathogenesis of dengue during the early phase of infection.https://www.frontiersin.org/article/10.3389/fimmu.2019.02500/fulldengue virusregulatory B cells (Bregs)immunopathogenesis of dengueplasmacellsIL-10B cell subsets |
| spellingShingle | Vinit Upasani Vinit Upasani Hoa Thi My Vo Sivlin Ung Sothy Heng Denis Laurent Rithy Choeung Veasna Duong Sopheak Sorn Sowath Ly Izabela A. Rodenhuis-Zybert Philippe Dussart Tineke Cantaert Impaired Antibody-Independent Immune Response of B Cells in Patients With Acute Dengue Infection Frontiers in Immunology dengue virus regulatory B cells (Bregs) immunopathogenesis of dengue plasmacells IL-10 B cell subsets |
| title | Impaired Antibody-Independent Immune Response of B Cells in Patients With Acute Dengue Infection |
| title_full | Impaired Antibody-Independent Immune Response of B Cells in Patients With Acute Dengue Infection |
| title_fullStr | Impaired Antibody-Independent Immune Response of B Cells in Patients With Acute Dengue Infection |
| title_full_unstemmed | Impaired Antibody-Independent Immune Response of B Cells in Patients With Acute Dengue Infection |
| title_short | Impaired Antibody-Independent Immune Response of B Cells in Patients With Acute Dengue Infection |
| title_sort | impaired antibody independent immune response of b cells in patients with acute dengue infection |
| topic | dengue virus regulatory B cells (Bregs) immunopathogenesis of dengue plasmacells IL-10 B cell subsets |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.02500/full |
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