Anti-tuberculosis chemotherapy alters TNFR2 expression on CD4+ lymphocytes in both drug-sensitive and -resistant tuberculosis: however, only drug-resistant tuberculosis maintains a pro-inflammatory profile after a long time
Abstract Background Tuberculosis (TB) is an infectious disease. During TB, regulatory T cells (Treg) are related to poor prognosis. However, information about conventional and unconventional Treg (cTreg and uTreg, respectively) is limited. The tumour necrosis factor (TNF) and its receptors (TNFR1 an...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-07-01
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| Series: | Molecular Medicine |
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| Online Access: | https://doi.org/10.1186/s10020-021-00320-4 |
| _version_ | 1818882275153018880 |
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| author | Norma A. Téllez-Navarrete Lucero A. Ramon-Luing Marcela Muñoz-Torrico Mario Preciado-García Karen Medina-Quero Rogelio Hernandez-Pando Leslie Chavez-Galan |
| author_facet | Norma A. Téllez-Navarrete Lucero A. Ramon-Luing Marcela Muñoz-Torrico Mario Preciado-García Karen Medina-Quero Rogelio Hernandez-Pando Leslie Chavez-Galan |
| author_sort | Norma A. Téllez-Navarrete |
| collection | DOAJ |
| description | Abstract Background Tuberculosis (TB) is an infectious disease. During TB, regulatory T cells (Treg) are related to poor prognosis. However, information about conventional and unconventional Treg (cTreg and uTreg, respectively) is limited. The tumour necrosis factor (TNF) and its receptors (TNFR1 and TNFR2) are necessary for mycobacterial infection, and TNFR2 signalling is required to maintain Treg. Methods A blood sample of drug-susceptible (DS-TB) and drug-resistant tuberculosis (DR-TB) patients was obtained before (basal) and after 2 and 6 months of anti-TB therapy. Expression of TNF, TNFR1, and TNFR2 (transmembrane form, tm) on cTreg, uTreg, activated CD4+ (actCD4+), and CD4+ CD25− (CD4+) T cell subpopulations were evaluated. The main objective was to identify immunological changes associated with sensitive/resistant Mtb strains and with the use of anti-TB therapy. Results We found that after 6 months of anti-TB therapy, both DS- and DR-TB patients have decreased the frequency of cTreg tmTNF+, CD4+ tmTNFR1+ and CD4+ tmTNFR2+. Nevertheless, after 6 months of therapy, only DR-TB patients decreased the frequency of actCD4+ tmTNF+ and actCD4+ tmTNFR2+, exhibited a systemic inflammatory status (high levels of TNF, IFN-γ and IL-12), and their purified CD4+ T cells showed that TNF and TNFR2 are up-regulated at the transcriptional level. Moreover, DS- and DR-TB down-regulated TNFR1 and other proteins associated with Treg (FOXP3 and TGFβ1) in response to the anti-TB therapy. Conclusion These results partially explain the differences in the immune response of DS-TB vs DR-TB. The frequency of actCD4+ tmTNFR2+ cells and inflammatory status should be considered in the follow-up of therapy in DR-TB patients. |
| first_indexed | 2024-12-19T15:15:10Z |
| format | Article |
| id | doaj.art-17cd49126dcd46bf9f245f566589fff5 |
| institution | Directory Open Access Journal |
| issn | 1076-1551 1528-3658 |
| language | English |
| last_indexed | 2024-12-19T15:15:10Z |
| publishDate | 2021-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Medicine |
| spelling | doaj.art-17cd49126dcd46bf9f245f566589fff52022-12-21T20:16:09ZengBMCMolecular Medicine1076-15511528-36582021-07-0127111410.1186/s10020-021-00320-4Anti-tuberculosis chemotherapy alters TNFR2 expression on CD4+ lymphocytes in both drug-sensitive and -resistant tuberculosis: however, only drug-resistant tuberculosis maintains a pro-inflammatory profile after a long timeNorma A. Téllez-Navarrete0Lucero A. Ramon-Luing1Marcela Muñoz-Torrico2Mario Preciado-García3Karen Medina-Quero4Rogelio Hernandez-Pando5Leslie Chavez-Galan6Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”Clinic of Tuberculosis, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”Laboratory of Immunology, Escuela Militar de Graduados en SanidadExperimental Pathology Section, Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador ZubiránLaboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”Abstract Background Tuberculosis (TB) is an infectious disease. During TB, regulatory T cells (Treg) are related to poor prognosis. However, information about conventional and unconventional Treg (cTreg and uTreg, respectively) is limited. The tumour necrosis factor (TNF) and its receptors (TNFR1 and TNFR2) are necessary for mycobacterial infection, and TNFR2 signalling is required to maintain Treg. Methods A blood sample of drug-susceptible (DS-TB) and drug-resistant tuberculosis (DR-TB) patients was obtained before (basal) and after 2 and 6 months of anti-TB therapy. Expression of TNF, TNFR1, and TNFR2 (transmembrane form, tm) on cTreg, uTreg, activated CD4+ (actCD4+), and CD4+ CD25− (CD4+) T cell subpopulations were evaluated. The main objective was to identify immunological changes associated with sensitive/resistant Mtb strains and with the use of anti-TB therapy. Results We found that after 6 months of anti-TB therapy, both DS- and DR-TB patients have decreased the frequency of cTreg tmTNF+, CD4+ tmTNFR1+ and CD4+ tmTNFR2+. Nevertheless, after 6 months of therapy, only DR-TB patients decreased the frequency of actCD4+ tmTNF+ and actCD4+ tmTNFR2+, exhibited a systemic inflammatory status (high levels of TNF, IFN-γ and IL-12), and their purified CD4+ T cells showed that TNF and TNFR2 are up-regulated at the transcriptional level. Moreover, DS- and DR-TB down-regulated TNFR1 and other proteins associated with Treg (FOXP3 and TGFβ1) in response to the anti-TB therapy. Conclusion These results partially explain the differences in the immune response of DS-TB vs DR-TB. The frequency of actCD4+ tmTNFR2+ cells and inflammatory status should be considered in the follow-up of therapy in DR-TB patients.https://doi.org/10.1186/s10020-021-00320-4TuberculosisDrug-resistanceTregsReceptorsTNF |
| spellingShingle | Norma A. Téllez-Navarrete Lucero A. Ramon-Luing Marcela Muñoz-Torrico Mario Preciado-García Karen Medina-Quero Rogelio Hernandez-Pando Leslie Chavez-Galan Anti-tuberculosis chemotherapy alters TNFR2 expression on CD4+ lymphocytes in both drug-sensitive and -resistant tuberculosis: however, only drug-resistant tuberculosis maintains a pro-inflammatory profile after a long time Molecular Medicine Tuberculosis Drug-resistance Tregs Receptors TNF |
| title | Anti-tuberculosis chemotherapy alters TNFR2 expression on CD4+ lymphocytes in both drug-sensitive and -resistant tuberculosis: however, only drug-resistant tuberculosis maintains a pro-inflammatory profile after a long time |
| title_full | Anti-tuberculosis chemotherapy alters TNFR2 expression on CD4+ lymphocytes in both drug-sensitive and -resistant tuberculosis: however, only drug-resistant tuberculosis maintains a pro-inflammatory profile after a long time |
| title_fullStr | Anti-tuberculosis chemotherapy alters TNFR2 expression on CD4+ lymphocytes in both drug-sensitive and -resistant tuberculosis: however, only drug-resistant tuberculosis maintains a pro-inflammatory profile after a long time |
| title_full_unstemmed | Anti-tuberculosis chemotherapy alters TNFR2 expression on CD4+ lymphocytes in both drug-sensitive and -resistant tuberculosis: however, only drug-resistant tuberculosis maintains a pro-inflammatory profile after a long time |
| title_short | Anti-tuberculosis chemotherapy alters TNFR2 expression on CD4+ lymphocytes in both drug-sensitive and -resistant tuberculosis: however, only drug-resistant tuberculosis maintains a pro-inflammatory profile after a long time |
| title_sort | anti tuberculosis chemotherapy alters tnfr2 expression on cd4 lymphocytes in both drug sensitive and resistant tuberculosis however only drug resistant tuberculosis maintains a pro inflammatory profile after a long time |
| topic | Tuberculosis Drug-resistance Tregs Receptors TNF |
| url | https://doi.org/10.1186/s10020-021-00320-4 |
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