Decreased MIP-3α Production from Antigen-Activated PBMCs in Symptomatic HIV-Infected Subjects
CD4<sup>+</sup> CCR6<sup>+</sup> T cells are highly susceptible to HIV infection, and a high cytokine producing CCR6<sup>+</sup> T cell subset is selectively lost during HIV infection. The CCR6 chemokine MIP-3α (CCL20) is produced at sites of infection in SIV anim...
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MDPI AG
2021-12-01
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| Online Access: | https://www.mdpi.com/2076-0817/11/1/7 |
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| author | Fuchun Zhang Lingling Sun Mark K. Lafferty Joseph B. Margolick Alfredo Garzino-Demo |
| author_facet | Fuchun Zhang Lingling Sun Mark K. Lafferty Joseph B. Margolick Alfredo Garzino-Demo |
| author_sort | Fuchun Zhang |
| collection | DOAJ |
| description | CD4<sup>+</sup> CCR6<sup>+</sup> T cells are highly susceptible to HIV infection, and a high cytokine producing CCR6<sup>+</sup> T cell subset is selectively lost during HIV infection. The CCR6 chemokine MIP-3α (CCL20) is produced at sites of infection in SIV animal models. Recently, we have shown that MIP-3α inhibits HIV replication. This inhibition of HIV infection is mediated by CCR6 signaling and eventuates in increased APOBEC3G expression. Since there are few existing reports on the role of MIP-3α in health or disease, we studied its production by PBMCs from HIV-seronegative and HIV+ subjects. We evaluated the ability of PBMCs to produce MIP-3α in response to antigen stimulation using cells obtained from two groups: one composed of HIV-seronegative subjects (n = 16) and the other composed of HIV+ subjects (n = 58), some asymptomatic and some with clinically defined AIDS. Antigens included fragment C of the tetanus toxin, <i>Candida albicans</i>, whole-inactivated HIV, and HIV p24. MIP-3α was detected by ELISA in tissue culture supernatants of antigen-stimulated PBMCs. MIP-3α production by antigen-stimulated PBMCs was readily measured for HIV-negative subjects and for HIV-seropositive asymptomatic subjects, but not for patients with AIDS. These results suggest that subversion of the MIP-3α-CCR6 axis by HIV during the course of infection contributes to the loss of immune function that eventually leads to AIDS. |
| first_indexed | 2024-03-10T00:46:36Z |
| format | Article |
| id | doaj.art-f20b4cabd7a143b88ae2e125d20f712f |
| institution | Directory Open Access Journal |
| issn | 2076-0817 |
| language | English |
| last_indexed | 2024-03-10T00:46:36Z |
| publishDate | 2021-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pathogens |
| spelling | doaj.art-f20b4cabd7a143b88ae2e125d20f712f2023-11-23T14:58:57ZengMDPI AGPathogens2076-08172021-12-01111710.3390/pathogens11010007Decreased MIP-3α Production from Antigen-Activated PBMCs in Symptomatic HIV-Infected SubjectsFuchun Zhang0Lingling Sun1Mark K. Lafferty2Joseph B. Margolick3Alfredo Garzino-Demo4Laboratory of Virus-Host Interactions, Division of Virology, Pathogenesis, and Cancer, Institute of Human Virology, Department of Microbiology and Immunology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USALaboratory of Virus-Host Interactions, Division of Virology, Pathogenesis, and Cancer, Institute of Human Virology, Department of Microbiology and Immunology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USALaboratory of Virus-Host Interactions, Division of Virology, Pathogenesis, and Cancer, Institute of Human Virology, Department of Microbiology and Immunology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USADepartment of Molecular Microbiology and Immunology, The Johns Hopkins Bloomberg School of Public Health, 615 North Wolfe Street, Baltimore, MD 21205, USALaboratory of Virus-Host Interactions, Division of Virology, Pathogenesis, and Cancer, Institute of Human Virology, Department of Microbiology and Immunology, University of Maryland School of Medicine, 725 West Lombard Street, Baltimore, MD 21201, USACD4<sup>+</sup> CCR6<sup>+</sup> T cells are highly susceptible to HIV infection, and a high cytokine producing CCR6<sup>+</sup> T cell subset is selectively lost during HIV infection. The CCR6 chemokine MIP-3α (CCL20) is produced at sites of infection in SIV animal models. Recently, we have shown that MIP-3α inhibits HIV replication. This inhibition of HIV infection is mediated by CCR6 signaling and eventuates in increased APOBEC3G expression. Since there are few existing reports on the role of MIP-3α in health or disease, we studied its production by PBMCs from HIV-seronegative and HIV+ subjects. We evaluated the ability of PBMCs to produce MIP-3α in response to antigen stimulation using cells obtained from two groups: one composed of HIV-seronegative subjects (n = 16) and the other composed of HIV+ subjects (n = 58), some asymptomatic and some with clinically defined AIDS. Antigens included fragment C of the tetanus toxin, <i>Candida albicans</i>, whole-inactivated HIV, and HIV p24. MIP-3α was detected by ELISA in tissue culture supernatants of antigen-stimulated PBMCs. MIP-3α production by antigen-stimulated PBMCs was readily measured for HIV-negative subjects and for HIV-seropositive asymptomatic subjects, but not for patients with AIDS. These results suggest that subversion of the MIP-3α-CCR6 axis by HIV during the course of infection contributes to the loss of immune function that eventually leads to AIDS.https://www.mdpi.com/2076-0817/11/1/7CCR6MIP-3αimmune responseantigen stimulationTh17 |
| spellingShingle | Fuchun Zhang Lingling Sun Mark K. Lafferty Joseph B. Margolick Alfredo Garzino-Demo Decreased MIP-3α Production from Antigen-Activated PBMCs in Symptomatic HIV-Infected Subjects Pathogens CCR6 MIP-3α immune response antigen stimulation Th17 |
| title | Decreased MIP-3α Production from Antigen-Activated PBMCs in Symptomatic HIV-Infected Subjects |
| title_full | Decreased MIP-3α Production from Antigen-Activated PBMCs in Symptomatic HIV-Infected Subjects |
| title_fullStr | Decreased MIP-3α Production from Antigen-Activated PBMCs in Symptomatic HIV-Infected Subjects |
| title_full_unstemmed | Decreased MIP-3α Production from Antigen-Activated PBMCs in Symptomatic HIV-Infected Subjects |
| title_short | Decreased MIP-3α Production from Antigen-Activated PBMCs in Symptomatic HIV-Infected Subjects |
| title_sort | decreased mip 3α production from antigen activated pbmcs in symptomatic hiv infected subjects |
| topic | CCR6 MIP-3α immune response antigen stimulation Th17 |
| url | https://www.mdpi.com/2076-0817/11/1/7 |
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