Téllez‑Navarrete et al. Mol Med (2021) 27:76 https://doi.org/10.1186/s10020‑021‑00320‑4 RESEARCH ARTICLE Anti‑tuberculosis chemotherapy alters TNFR2 expression on CD4+ lymphocytes in both drug‑sensitive and ‑resistant tuberculosis: however, only drug‑resistant tuberculosis maintains a pro‑infammatory profle after a long time Norma A. Téllez-Navarrete 1 , Lucero A. Ramon-Luing 1 , Marcela Muñoz-Torrico 2 , Mario Preciado-García 1 , Karen Medina-Quero 3 , Rogelio Hernandez-Pando 4 and Leslie Chavez-Galan 1* Abstract Background: Tuberculosis (TB) is an infectious disease. During TB, regulatory T cells (Treg) are related to poor prog- nosis. 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-regu- lated 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. © The Author(s) 2021. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. Open Access Molecular Medicine *Correspondence: lchavez_galan@iner.gob.mx 1 Laboratory of Integrative Immunology, Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas”, Calzada de Tlalpan No. 4510, CP. 14080 Mexico City, Mexico Full list of author information is available at the end of the article