ORIGINAL RESEARCH article
Front. Immunol.
Sec. Microbial Immunology
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1591026
Antimycobacterial and immunomodulatory activities of sorafenib in mice preclinical model of TB infection through CD4 + CD25 low and CD8 + CD25 low effector T cells
Provisionally accepted
- Indian Institute of Science (IISc), Bangalore, India
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Tuberculosis is a communicable disease caused by Mycobacterium tuberculosis (Mtb). It is one of the major global public health problems that leads to a high morbidity and mortality rate.Drug resistance in Mycobacterium tuberculosis (Mtb) is another significant and persistent public health concern. The development of effective TB vaccines and treatments requires a better understanding of the intricate interactions between M. tuberculosis and host immunity.We previously reported that sorafenib (SRB) reduces bacterial growth by allosterically inhibiting ornithine acetyltransferase (MtArgJ), an essential enzyme in the arginine biosynthesis pathway of Mtb. Here, we report on the antimicrobial activity of sorafenib in preclinical mouse models of tuberculosis. Sorafenib is a potent drug approved by the Food and Drug Administration (FDA) for treating several types of cancer. The current study is focused on the immunomodulation that SRB induces in the host, specifically the immunological response that is triggered to combat the pathogenicity and survival of the bacteria.Here, we show that SRB significantly sterilizes the bacterial burden in chronic infection animal models of tuberculosis by reducing the number of Mtb-susceptible alveolar macrophages (AMs), and that SRB is more effective when combined with rifampicin (RIF). In the current study, we documented a new immune modulatory characteristic of sorafenib that, upon SRB treatment, markedly increased effector T cells (Teff -CD4 + CD25 low and CD8 + CD25 low ) activity and decreased regulatory T cells, the immunosuppressive T cells (Treg-CD4 + CD25 high and CD8 + CD25 high ) function. In conclusion, our studies revealed that SRB is beneficial for both boosting an efficient T cell response and lowering the tubercular load.
Keywords: Mycobacterium tuberculosis (MTB), Sorafenib (SRB), Immunomodulation, alveolar macrophages (AMs), T cells
Received: 10 Mar 2025; Accepted: 04 Jul 2025.
Copyright: © 2025 RAJMANI and Surolia. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Raju S RAJMANI, Indian Institute of Science (IISc), Bangalore, India
Avadhesha Surolia, Indian Institute of Science (IISc), Bangalore, India
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