Mahadik, Kasturi and Prakhar, Praveen and Rajmani, R S and Singh, Amit and Balaji, Kithiganahalli Narayanaswamy (2018) c-Abl-TWIST1 Epigenetically Dysregulate Inflammatory Responses during Mycobacterial Infection by Co-Regulating Bone Morphogenesis Protein and miR27a. In: FRONTIERS IN IMMUNOLOGY, 9 .
Full text not available from this repository. (Request a copy)Abstract
Mycobacteria propelled modulation of host responses is of considerable interest in the face of emerging drug resistance. Although it is known that Abl tyrosine kinases affect entry and persistence of mycobacteria, mechanisms that couple c-Abl to proximal signaling pathways during immunity are poorly understood. Loss-of-function of c-Abl through Imatinib, in a mouse model of tuberculosis or RNA interference, identified bone morphogenesis protein (BMP) signaling as its cellular target. We demonstrate that c-Abl promotes mycobacterial survival through epigenetic modification brought about by KAT5-TWIST1 at Bmp loci. c-Abl-BMP signaling deregulated iNOS, aggravating the inflammatory balance. Interestingly, BMP signaling was observed to have far-reaching effects on host immunity, as it attenuated TLR3 pathway by engaging miR27a. Significantly, these events were largely mediated via WhiB3 and DosR/S/T but not SecA signaling pathway of mycobacteria. Our findings suggest molecular mechanisms of host pathways hijacked by mycobacteria and expand our understanding of c-Abl inhibitors in potentiating innate immune responses.
| Item Type: | Journal Article |
|---|---|
| Publication: | FRONTIERS IN IMMUNOLOGY |
| Additional Information: | Copy right for this article belong to the FRONTIERS MEDIA SA, PO BOX 110, EPFL INNOVATION PARK, BUILDING I, LAUSANNE, 1015, SWITZERLAND |
| Department/Centre: | Division of Biological Sciences > Microbiology & Cell Biology Division of Biological Sciences > Centre for Infectious Disease Research |
| Date Deposited: | 02 Mar 2018 15:04 |
| Last Modified: | 02 Mar 2018 15:04 |
| URI: | http://eprints.iisc.ac.in/id/eprint/58937 |
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