ABSTRACT Bacillus cereus endophthalmitis is a rapidly progressing intraocular infection that often results in poor visual outcomes due to extensive retinal damage. Microglia are resident innate immune cells in the brain and retina that play critical roles in neurological and ocular diseases. To investigate the functional role and mechanisms of microglia during B. cereus infection, we established an in vitro microglial infection model using murine BV2 and human HMC3 cells. B. cereus infection reduced microglial viability and induced membrane rupture. Transcriptome analysis revealed enrichment of inflammatory and cell death. Flow cytometric screening identified that the RIPK1 inhibitor Nec‐1 rescued cell death. Mechanistically, B. cereus increased phosphorylation of RIPK3 and MLKL, which was abolished by Nec‐1. Moreover, Nec‐1 suppressed B. cereus ‐induced secretion of IL‐1β, IL‐6, and TNF‐α. In summary, this study demonstrates that B. cereus induces microglial necroptosis by activating the RIPK3/MLKL pathway, providing a new mechanism for neuroinflammation caused by related infections.
Yang et al. (Thu,) studied this question.