<i>Mycobacterium tuberculosis</i> Acr1 Protein Mitigates Experimental Autoimmune Encephalomyelitis Symptoms by Generating Myeloid‐Derived Suppressor Cells and Regulatory T Cells
Mycobacterium tuberculosis (Mtb) effectively suppresses host immunity to ensure its survival. We have earlier shown that the Acr1 protein of Mtb can inhibit the differentiation of dendritic cells (DCs). Consequently, in the current study, we examined the role of Acr1 in mitigating autoimmunity. Initially, we observed that Acr1 skews the differentiation of DCs into functionally competent myeloid-derived suppressor cells (MDSC<sup>Acr1</sup>) that chiefly secrete immunosuppressive molecules, expand regulatory T cells (Treg<sup>Acr1</sup>) and attenuate inflammatory responses. Further, MDSC<sup>Acr1</sup> suppress Th17 cells. Acr1 expanded MDSCs with a concurrent increase in myelin oligodendrocyte glycoprotein (MOG)-specific Tregs and a decline in Th17 cells in a murine experimental autoimmune encephalomyelitis (EAE) model and prevented the onset of the disease. These results were further validated in the prophylactic model of EAE. Mechanistically, Acr1 activates Tregs and MDSCs via the TLR-4 pathway, implicating innate immune recognition in Mtb-induced suppression. The results indicate a potential role of Acr1 against autoimmune diseases.
Authors
- Javed Naim Agrewala (ORCID: https://orcid.org/0000-0003-0227-1042)
- Sharvan Sehrawat (ORCID: https://orcid.org/0000-0001-5745-6955)
- Sidhanta Nanda (ORCID: https://orcid.org/0000-0002-1577-8195)
- Mohammad Adeel Zafar (ORCID: https://orcid.org/0000-0002-7029-2489)
- Ashish Arora (ORCID: https://orcid.org/0000-0002-0630-2224)
- Sanpreet Singh (ORCID: https://orcid.org/0000-0002-6930-5430)
- Taruna Lamba
- Suneel Prajapati (ORCID: https://orcid.org/0000-0002-5249-9865)
- Kaneez F. Siddiqui
- Mohammad Shaaz
- Sudhakar Singh
- Jitendra K. Malik
- Mohd Affan Khan
Institutions
- Indian Institute of Technology Ropar (IN)
- Indian Institute of Science Education and Research Mohali (IN)
- Central Drug Research Institute (IN)
- Institute of Microbial Technology (IN)
Publication Details
- Journal
- Immunology
- Published
- 2025-10-19
- DOI
- https://doi.org/10.1111/imm.70050
- Primary Topic
- Immune cells in cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Emory University
- Department of Science and Technology, Ministry of Science and Technology, India
- Indian Council of Medical Research
- Ministry of Education, India
- Indian Institute of Science Education and Research Mohali
- Indian Institute of Technology Ropar
- Scheme for Promotion of Academic and Research Collaboration
- National Institutes of Health