Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

The coordinated outcome of STIM1-Orai1 and superoxide signalling is crucial for headkidney macrophage apoptosis and clearance of Mycobacterium fortuitum

Dahiya, Priyanka ; Datta, Debika ; Hussain, Md Arafat ; Verma, Gaurav LU ; Shelly, Asha ; Mehta, Priyanka and Mazumder, Shibnath (2021) In Developmental and Comparative Immunology 114.
Abstract

The mechanisms underlying M. fortuitum-induced pathogenesis remains elusive. Using headkidney macrophages (HKM) from Clarias gariepinus, we report that TLR-2-mediated internalization of M. fortuitum is imperative to the induction of pathogenic effects. Inhibiting TLR-2 signalling alleviated HKM apoptosis, thereby favouring bacterial survival. Additionally, TLR-2-mediated cytosolic calcium (Ca2+)c elevation was instrumental for eliciting ER-stress in infected HKM. ER-stress triggered the activation of membrane-proximal calcium entry channels comprising stromal interaction molecule 1 (STIM1) and calcium-release activated calcium channel 1 (Orai1). RNAi studies suggested STIM1-Orai1 signalling initiate... (More)

The mechanisms underlying M. fortuitum-induced pathogenesis remains elusive. Using headkidney macrophages (HKM) from Clarias gariepinus, we report that TLR-2-mediated internalization of M. fortuitum is imperative to the induction of pathogenic effects. Inhibiting TLR-2 signalling alleviated HKM apoptosis, thereby favouring bacterial survival. Additionally, TLR-2-mediated cytosolic calcium (Ca2+)c elevation was instrumental for eliciting ER-stress in infected HKM. ER-stress triggered the activation of membrane-proximal calcium entry channels comprising stromal interaction molecule 1 (STIM1) and calcium-release activated calcium channel 1 (Orai1). RNAi studies suggested STIM1-Orai1 signalling initiate calpain-mediated cleavage of nitric oxide synthase interacting protein, prompting the release of pro-apoptotic nitric oxide. Inhibiting STIM1-Orai1 signalling attenuated superoxide production (O2•–) and vice versa. We conclude, TLR-2-induced ER-stress triggers STIM1/Orai1 expression and that the reciprocal association between STIM1-Orai1 signalling and oxidative stress is critical for sustaining (Ca2+)c level, thereby prolonging ER-stress and maintenance of pro-oxidant rich environment to induce HKM apoptosis and bacterial clearance.

(Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Calpain, ER-Stress, NOSIP, SOCE, Superoxide, TLR-2
in
Developmental and Comparative Immunology
volume
114
article number
103800
publisher
Elsevier
external identifiers
  • scopus:85089462333
  • pmid:32771347
ISSN
0145-305X
DOI
10.1016/j.dci.2020.103800
language
English
LU publication?
yes
id
4af76212-ee8e-414a-9fce-45ec43d6163c
date added to LUP
2020-08-27 09:21:58
date last changed
2024-06-26 21:06:36
@article{4af76212-ee8e-414a-9fce-45ec43d6163c,
  abstract     = {{<p>The mechanisms underlying M. fortuitum-induced pathogenesis remains elusive. Using headkidney macrophages (HKM) from Clarias gariepinus, we report that TLR-2-mediated internalization of M. fortuitum is imperative to the induction of pathogenic effects. Inhibiting TLR-2 signalling alleviated HKM apoptosis, thereby favouring bacterial survival. Additionally, TLR-2-mediated cytosolic calcium (Ca<sup>2+</sup>)<sub>c</sub> elevation was instrumental for eliciting ER-stress in infected HKM. ER-stress triggered the activation of membrane-proximal calcium entry channels comprising stromal interaction molecule 1 (STIM1) and calcium-release activated calcium channel 1 (Orai1). RNAi studies suggested STIM1-Orai1 signalling initiate calpain-mediated cleavage of nitric oxide synthase interacting protein, prompting the release of pro-apoptotic nitric oxide. Inhibiting STIM1-Orai1 signalling attenuated superoxide production (O<sub>2</sub><sup>•–</sup>) and vice versa. We conclude, TLR-2-induced ER-stress triggers STIM1/Orai1 expression and that the reciprocal association between STIM1-Orai1 signalling and oxidative stress is critical for sustaining (Ca<sup>2+</sup>)<sub>c</sub> level, thereby prolonging ER-stress and maintenance of pro-oxidant rich environment to induce HKM apoptosis and bacterial clearance.</p>}},
  author       = {{Dahiya, Priyanka and Datta, Debika and Hussain, Md Arafat and Verma, Gaurav and Shelly, Asha and Mehta, Priyanka and Mazumder, Shibnath}},
  issn         = {{0145-305X}},
  keywords     = {{Calpain; ER-Stress; NOSIP; SOCE; Superoxide; TLR-2}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Developmental and Comparative Immunology}},
  title        = {{The coordinated outcome of STIM1-Orai1 and superoxide signalling is crucial for headkidney macrophage apoptosis and clearance of Mycobacterium fortuitum}},
  url          = {{http://dx.doi.org/10.1016/j.dci.2020.103800}},
  doi          = {{10.1016/j.dci.2020.103800}},
  volume       = {{114}},
  year         = {{2021}},
}