1. VapC12 ribonuclease toxin modulates host immune response during Mycobacterium tuberculosis infection.
- Author
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Tyagi S, Sadhu S, Sharma T, Paul A, Pandey M, Nain VK, Rathore DK, Chatterjee S, Awasthi A, and Pandey AK
- Subjects
- Animals, Mice, Immunity, Innate, Phenotype, Toxins, Biological, Mycobacterium tuberculosis genetics, Mycobacterium tuberculosis pathogenicity, Tuberculosis immunology, Tuberculosis metabolism, Ribonucleases genetics, Ribonucleases metabolism
- Abstract
Mechanistic understanding of antibiotic persistence is a prerequisite in controlling the emergence of MDR cases in Tuberculosis (TB). We have reported that the cholesterol-induced activation of VapC12 ribonuclease is critical for disease persistence in TB. In this study, we observed that relative to the wild type, mice infected with Δ vapC12 induced a pro-inflammatory response, had a higher pathogen load, and responded better to the anti-TB treatment. In a high-dose infection model, all the mice infected with Δ vapC12 succumbed early to the disease. Finally, we reported that the above phenotype of Δ vapC12 was dependent on the presence of the TLR4 receptor. Overall, the data suggests that failure of a timely resolution of the early inflammation by the Δ vapC12 infected mice led to hyperinflammation, altered T-cell response and high bacterial load. In conclusion, our findings suggest the role of the VapC12 toxin in modulating the innate immune response of the host in ways that favor the long-term survival of the pathogen inside the host., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Tyagi, Sadhu, Sharma, Paul, Pandey, Nain, Rathore, Chatterjee, Awasthi and Pandey.)
- Published
- 2024
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