Macrophage Migration Inhibitory Factor (MIF) Promotes Increased Proportions of the Highly Permissive Th17-like Cell Profile during HIV Infection
In this study, we evaluate the role of the MIF/CD74 axis in the functionality of CD4<sup>+</sup> T lymphocytes (CD4TL) during HIV infection. MDMs from healthy donors were infected with a R5-tropic or Transmitted/Founder (T/F) HIV strain. At day 11 post-MDM infection, allogeneic co-cultur...
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| Language: | English |
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MDPI AG
2022-10-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/14/10/2218 |
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| author | César Trifone Lucía Baquero Alejandro Czernikier Paula Benencio Lin Leng Natalia Laufer María Florencia Quiroga Richard Bucala Yanina Ghiglione Gabriela Turk |
| author_facet | César Trifone Lucía Baquero Alejandro Czernikier Paula Benencio Lin Leng Natalia Laufer María Florencia Quiroga Richard Bucala Yanina Ghiglione Gabriela Turk |
| author_sort | César Trifone |
| collection | DOAJ |
| description | In this study, we evaluate the role of the MIF/CD74 axis in the functionality of CD4<sup>+</sup> T lymphocytes (CD4TL) during HIV infection. MDMs from healthy donors were infected with a R5-tropic or Transmitted/Founder (T/F) HIV strain. At day 11 post-MDM infection, allogeneic co-cultures with uninfected CD4TLs plus MIF stimulus were performed. Cytokine production was evaluated by ELISA. MIF plasma levels of people with HIV (PWH) were evaluated by ELISA. The phenotype and infection rate of CD4TLs from PWH were analyzed after MIF stimulus. Intracellular cytokines and transcription factors were evaluated by flow cytometry. Data were analyzed by parametric or non-parametric methods. The MIF stimulation of HIV-infected MDMs induced an increased expression of IL-6, IL-1β and IL-8. In CD4TL/MDM co-cultures, the MIF treatment increased IL-17A/RORγt-expressing CD4TLs. Higher concentrations of IL-17A in supernatants were also observed. These results were recapitulated using transmitted/founder (T/F) HIV-1 strains. The MIF treatment appeared to affect memory CD4TLs more than naïve CD4TLs. MIF blocking showed a negative impact on IL17A<sup>+</sup>CD4TL proportions. Higher MIF concentrations in PWH-derived plasma were correlated with higher IL-17A<sup>+</sup>CD4TL percentages. Finally, MIF stimulation in PWH-derived PBMCs led to an increase in Th17-like population. MIF may contribute to viral pathogenesis by generating a microenvironment enriched in activating mediators and Th17-like CD4TLs, which are known to be highly susceptible to HIV-1 infection and relevant to viral persistence. These observations establish a basis for considering MIF as a possible therapeutic target. |
| first_indexed | 2024-03-09T19:23:29Z |
| format | Article |
| id | doaj.art-f947b2e0e6904eb2a209cfe697b58023 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T19:23:29Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-f947b2e0e6904eb2a209cfe697b580232023-11-24T03:09:35ZengMDPI AGViruses1999-49152022-10-011410221810.3390/v14102218Macrophage Migration Inhibitory Factor (MIF) Promotes Increased Proportions of the Highly Permissive Th17-like Cell Profile during HIV InfectionCésar Trifone0Lucía Baquero1Alejandro Czernikier2Paula Benencio3Lin Leng4Natalia Laufer5María Florencia Quiroga6Richard Bucala7Yanina Ghiglione8Gabriela Turk9Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1121ABG, ArgentinaInstituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), CONICET—Universidad de Buenos Aires, Buenos Aires C1121ABG, ArgentinaFacultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1121ABG, ArgentinaFacultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1121ABG, ArgentinaDepartment of Medicine, Yale University School of Medicine, New Haven, CT 06510, USAInstituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), CONICET—Universidad de Buenos Aires, Buenos Aires C1121ABG, ArgentinaInstituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), CONICET—Universidad de Buenos Aires, Buenos Aires C1121ABG, ArgentinaDepartment of Medicine, Yale University School of Medicine, New Haven, CT 06510, USAFacultad de Medicina, Universidad de Buenos Aires, Buenos Aires C1121ABG, ArgentinaInstituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), CONICET—Universidad de Buenos Aires, Buenos Aires C1121ABG, ArgentinaIn this study, we evaluate the role of the MIF/CD74 axis in the functionality of CD4<sup>+</sup> T lymphocytes (CD4TL) during HIV infection. MDMs from healthy donors were infected with a R5-tropic or Transmitted/Founder (T/F) HIV strain. At day 11 post-MDM infection, allogeneic co-cultures with uninfected CD4TLs plus MIF stimulus were performed. Cytokine production was evaluated by ELISA. MIF plasma levels of people with HIV (PWH) were evaluated by ELISA. The phenotype and infection rate of CD4TLs from PWH were analyzed after MIF stimulus. Intracellular cytokines and transcription factors were evaluated by flow cytometry. Data were analyzed by parametric or non-parametric methods. The MIF stimulation of HIV-infected MDMs induced an increased expression of IL-6, IL-1β and IL-8. In CD4TL/MDM co-cultures, the MIF treatment increased IL-17A/RORγt-expressing CD4TLs. Higher concentrations of IL-17A in supernatants were also observed. These results were recapitulated using transmitted/founder (T/F) HIV-1 strains. The MIF treatment appeared to affect memory CD4TLs more than naïve CD4TLs. MIF blocking showed a negative impact on IL17A<sup>+</sup>CD4TL proportions. Higher MIF concentrations in PWH-derived plasma were correlated with higher IL-17A<sup>+</sup>CD4TL percentages. Finally, MIF stimulation in PWH-derived PBMCs led to an increase in Th17-like population. MIF may contribute to viral pathogenesis by generating a microenvironment enriched in activating mediators and Th17-like CD4TLs, which are known to be highly susceptible to HIV-1 infection and relevant to viral persistence. These observations establish a basis for considering MIF as a possible therapeutic target.https://www.mdpi.com/1999-4915/14/10/2218HIVMIFMDM/CD4TL co-cultureimmune pathogenesis |
| spellingShingle | César Trifone Lucía Baquero Alejandro Czernikier Paula Benencio Lin Leng Natalia Laufer María Florencia Quiroga Richard Bucala Yanina Ghiglione Gabriela Turk Macrophage Migration Inhibitory Factor (MIF) Promotes Increased Proportions of the Highly Permissive Th17-like Cell Profile during HIV Infection Viruses HIV MIF MDM/CD4TL co-culture immune pathogenesis |
| title | Macrophage Migration Inhibitory Factor (MIF) Promotes Increased Proportions of the Highly Permissive Th17-like Cell Profile during HIV Infection |
| title_full | Macrophage Migration Inhibitory Factor (MIF) Promotes Increased Proportions of the Highly Permissive Th17-like Cell Profile during HIV Infection |
| title_fullStr | Macrophage Migration Inhibitory Factor (MIF) Promotes Increased Proportions of the Highly Permissive Th17-like Cell Profile during HIV Infection |
| title_full_unstemmed | Macrophage Migration Inhibitory Factor (MIF) Promotes Increased Proportions of the Highly Permissive Th17-like Cell Profile during HIV Infection |
| title_short | Macrophage Migration Inhibitory Factor (MIF) Promotes Increased Proportions of the Highly Permissive Th17-like Cell Profile during HIV Infection |
| title_sort | macrophage migration inhibitory factor mif promotes increased proportions of the highly permissive th17 like cell profile during hiv infection |
| topic | HIV MIF MDM/CD4TL co-culture immune pathogenesis |
| url | https://www.mdpi.com/1999-4915/14/10/2218 |
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