Open AccessThe secreted antigen, HP 0175, of H elicobacter pylori links the unfolded protein response ( UPR ) to autophagy in gastric epithelial cells
Author(s) -
Halder Priyanka,
Datta Chandreyee,
Kumar Ranjeet,
Sharma Arun Kumar,
Basu Joyoti,
Kundu Manikuntala
Publication year - 2015
Publication title -
cellular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.542
H-Index - 138
eISSN - 1462-5822
pISSN - 1462-5814
DOI - 10.1111/cmi.12396
Subject(s) - autophagy , biology , unfolded protein response , microbiology and biotechnology , apoptosis , gene silencing , autophagy related protein 13 , bag3 , kinase , protein kinase r , gene knockdown , protein kinase a , endoplasmic reticulum , gene , cyclin dependent kinase 2 , biochemistry
Summary Autophagy is an intracellular catabolic process that is required to maintain cellular homeostasis. Pathogen‐elicited host cell autophagy may favour containment of infection or may help in bacterial survival. Pathogens have developed the ability to modulate host autophagy. The secreted antigen HP 0175, a peptidyl prolyl cis,trans isomerase of H elicobacter pylori , has moonlighting functions with reference to host cells. Here we show that it executes autophagy in gastric epithelial cells. Autophagy is dependent on the unfolded protein response ( UPR ) that activates the expression of P KR ‐like ER k inase ( PERK ). This is accompanied by phosphorylation of eukaryotic initiation factor 2α ( eIF ‐2α) and transcriptional activation of ATF4 and CHOP . Knockdown of UPR ‐related genes inhibits the conversion of LC 3 I to LC 3 II , a marker of autophagy. The autophagy‐inducing ability of H . pylori is compromised when cells are infected with an isogenic hp0175 mutant. Autophagy precedes apoptosis. Silencing of BECLIN 1 augments cleavage of caspase 3 as well as apoptosis. Increased apoptosis of gastric epithelial cells is known to be linked to H . pylori ‐mediated gastric inflammation and carcinogenesis. To the best of our knowledge, this study provides the first demonstration of how HP 0175 endowed with moonlighting functions links UPR ‐dependent autophagy and apoptosis during H . pylori infection.