The coordinated outcome of STIM1-Orai1 and superoxide signalling is crucial for headkidney macrophage apoptosis and clearance of Mycobacterium fortuitum
(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.
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- author
- Dahiya, Priyanka ; Datta, Debika ; Hussain, Md Arafat ; Verma, Gaurav LU ; Shelly, Asha ; Mehta, Priyanka and Mazumder, Shibnath
- organization
- publishing date
- 2021
- 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
-
- pmid:32771347
- scopus:85089462333
- 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
- 2024-09-19 04:46:36
@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}}, }