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Selective inhibition of IFNG-induced autophagy by Mir155- and Mir31-responsive WNT5A and SHH signaling

Holla, Sahana and Kurowska-Stolarska, Mariola and Bayry, Jagadeesh and Balaji, Kithiganahalli Narayanaswamy (2014) Selective inhibition of IFNG-induced autophagy by Mir155- and Mir31-responsive WNT5A and SHH signaling. In: AUTOPHAGY, 10 (2). pp. 311-330.

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Official URL: http://dx.doi.org/10.4161/auto.27225


Autophagy is one of the major immune mechanisms engaged to clear intracellular infectious agents. However, several pathogens have evolved strategies to evade autophagy. Here, we demonstrated that Mycobacteria, Shigella, and Listeria but not Klebsiella, Staphylococcus, and Escherichia inhibit IFNG-induced autophagy in macrophages by evoking selective and robust activation of WNT and SHH pathways via MTOR. Utilization of gain- or loss-of-function analyses as well as mir155-null macrophages emphasized the role of MTOR-responsive epigenetic modifications in the induction of Mir155 and Mir31. Importantly, cellular levels of PP2A, a phosphatase, were regulated by Mir155 and Mir31 to fine-tune autophagy. Diminished expression of PP2A led to inhibition of GSK3B, thus facilitating the prolonged activation of WNT and SHH signaling pathways. Sustained WNT and SHH signaling effectuated the expression of anti-inflammatory lipoxygenases, which in tandem inhibited IFNG-induced JAK-STAT signaling and contributed to evasion of autophagy. Altogether, these results established a role for new host factors and inhibitory mechanisms employed by the pathogens to limit autophagy, which could be targeted for therapeutic interventions.

Item Type: Journal Article
Publication: AUTOPHAGY
Additional Information: Copyright for this article belongs to the LANDES BIOSCIENCE, USA
Keywords: autophagy; IFNG; WNT-SHH signaling; microRNA; lipoxygenase
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited: 11 Mar 2014 05:25
Last Modified: 11 Mar 2014 12:09
URI: http://eprints.iisc.ac.in/id/eprint/48546

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