A cytoprotective role for optineurin during mycobacterial infection of macrophages

• Published in: Biochemistry and biophysics reports 2024-07, Vol.38, p.101672-101672, Article 101672
• Main Authors: Ramachandran, Gopalakrishna, Yeruva, Chaitanya Veena, Swarup, Ghanshyam, Raghunand, Tirumalai R.
• Format: Article
• Language: English
• Subjects: Autophagy; Cell death; Cytoprotectivity; Macrophages; Mycobacteria; Optineurin
• ISSN: 2405-5808; 2405-5808
• DOI: 10.1016/j.bbrep.2024.101672

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-1β. 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. [Display omitted] •Mycobacterial infection induces increased cell death in Optineurin deficient BMDMs.•Infected Optineurin deficient macrophages display diminished autophagy.•Optineurin deficiency macrophages have disrupted inflammatory responses.•Its cytoprotective role makes Optineurin therapeutically relevant to TB infection.