Gogoi, Mayuri and Chandra, Kasturi and Sarikhani, Mohsen and Ramani, Ramya and Sundaresan, Nagalingam Ravi and Chakravortty, Dipshikha (2018) Salmonella escapes adaptive immune response via SIRT2 mediated modulation of innate immune response in dendritic cells. In: PLOS PATHOGENS, 14 (11).
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Abstract
Salmonella being a successful pathogen, employs a plethora of immune evasion mechanisms. This contributes to pathogenesis, persistence and also limits the efficacy of available treatment. All these contributing factors call upon for new drug targets against Salmonella. For the first time, we have demonstrated that Salmonella upregulates sirtuin 2 (SIRT2), an NAD(+) dependent deacetylase in dendritic cells (DC). SIRT2 upregulation results in translocation of NFKB p65 to the nucleus. This further upregulates NOS2 transcription and nitric oxide (NO) production. NO subsequently shows antibacterial activity and suppresses T cell proliferation. NOS2 mediated effect of SIRT2 is further validated by the absence of effect of SIRT2 inhibition in NOS2(-/-) mice. Inhibition of SIRT2 increases intracellular survival of the pathogen and enhances antigen presentation in vitro. However, in vivo SIRT2 inhibition shows lower bacterial organ burden and reduced tissue damage. SIRT2 knockout mice also demonstrate reduced bacterial organ burden compared to wild-type mice. Collectively, our results prove the role of SIRT2 in Salmonella pathogenesis and the mechanism of action. This can aid in designing of host-targeted therapeutics directed towards inhibition of SIRT2.
| Item Type: | Journal Article |
|---|---|
| Publication: | PLOS PATHOGENS |
| Publisher: | PUBLIC LIBRARY SCIENCE |
| Additional Information: | Copyright of this article belong to PUBLIC LIBRARY SCIENCE |
| Department/Centre: | Division of Biological Sciences > Microbiology & Cell Biology Division of Interdisciplinary Sciences > Centre for Biosystems Science and Engineering |
| Date Deposited: | 28 Dec 2018 06:11 |
| Last Modified: | 28 Dec 2018 06:11 |
| URI: | http://eprints.iisc.ac.in/id/eprint/61307 |
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