PMID- 38434142
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20240305
IS  - 2405-5808 (Electronic)
IS  - 2405-5808 (Linking)
VI  - 38
DP  - 2024 Jul
TI  - A cytoprotective role for optineurin during mycobacterial infection of 
      macrophages.
PG  - 101672
LID - 10.1016/j.bbrep.2024.101672 [doi]
LID - 101672
AB  - Autophagy has emerged as a critical innate immune mechanism for host elimination 
      of intracellular pathogens, however, the role of the autophagy receptor 
      Optineurin during mycobacterial infection is not fully understood. To address 
      this lacuna, we infected bone marrow-derived macrophages (BMDMs) derived from 
      Optn(+/+) and Optn(-/-) mice with Mycobacterium smegmatis, and observed the 
      infection outcome at sequential time points. While low multiplicity of infection 
      (MOI) did not show any significant difference between BMDMs from the two groups, 
      at high MOI Optn(-/-) mice-derived BMDMs showed significantly lower colony 
      forming unit counts, as well as lower cell counts at 12 h and 24 h 
      post-infection. Quantification of cell numbers and nuclear morphologies at 
      various time points post-infection indicated a markedly higher cell death in the 
      Optineurin-deficient macrophages. Optineurin-deficient BMDMs showed significantly 
      lower levels of the autophagosomal protein LC3-II upon infection, indicating a 
      potential role for Optineurin in regulating autophagy during mycobacterial 
      infection. Moreover, when stimulated by bacterial LPS, Optineurin deficient 
      macrophages, showed altered levels of the inflammatory cytokine pro-IL-1beta. These 
      observations taken together suggest a novel regulatory role for Optineurin during 
      mycobacterial infection. Its deficiency leads to an impairment in macrophage 
      responses, directly impacting the pathophysiology of infection.
CI  - (c) 2024 The Authors.
FAU - Ramachandran, Gopalakrishna
AU  - Ramachandran G
AD  - CSIR - Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500007, 
      India.
FAU - Yeruva, Chaitanya Veena
AU  - Yeruva CV
AD  - CSIR - Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500007, 
      India.
FAU - Swarup, Ghanshyam
AU  - Swarup G
AD  - CSIR - Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500007, 
      India.
AD  - Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
FAU - Raghunand, Tirumalai R
AU  - Raghunand TR
AD  - CSIR - Centre for Cellular and Molecular Biology, Uppal Road, Hyderabad, 500007, 
      India.
AD  - Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, 201002, India.
LA  - eng
PT  - Journal Article
DEP - 20240226
PL  - Netherlands
TA  - Biochem Biophys Rep
JT  - Biochemistry and biophysics reports
JID - 101660999
PMC - PMC10907145
OTO - NOTNLM
OT  - Autophagy
OT  - Cell death
OT  - Cytoprotectivity
OT  - Macrophages
OT  - Mycobacteria
OT  - Optineurin
COIS- The authors declare that they have no known competing financial interests or 
      personal relationships that could have appeared to influence the work reported in 
      this paper.
EDAT- 2024/03/04 06:50
MHDA- 2024/03/04 06:51
PMCR- 2024/02/26
CRDT- 2024/03/04 04:41
PHST- 2023/12/26 00:00 [received]
PHST- 2024/02/10 00:00 [revised]
PHST- 2024/02/20 00:00 [accepted]
PHST- 2024/03/04 06:51 [medline]
PHST- 2024/03/04 06:50 [pubmed]
PHST- 2024/03/04 04:41 [entrez]
PHST- 2024/02/26 00:00 [pmc-release]
AID - S2405-5808(24)00036-0 [pii]
AID - 101672 [pii]
AID - 10.1016/j.bbrep.2024.101672 [doi]
PST - epublish
SO  - Biochem Biophys Rep. 2024 Feb 26;38:101672. doi: 10.1016/j.bbrep.2024.101672. 
      eCollection 2024 Jul.