Abstract
Jellyfish stings induce a range of symptoms, from localized irritation to life-threatening systemic reactions, yet the underlying immune mechanisms remain poorly understood. This study employed single-cell RNA sequencing (scRNA-seq) to analyze peripheral blood mononuclear cells (PBMCs) from a severely affected patient and healthy controls, uncovering the immune landscape at single-cell resolution and identifying the signaling pathways. We identified 11 major immune cell types, with a marked increase in CD14+ monocytes (81.86% of total cells) and significant reductions in T cells, B cells, and CD16+ monocytes in the envenomated patient. Subclustering revealed six monocyte and four neutrophil subsets, each displaying distinct functional profiles. Patient monocytes were enriched for MMP9+ and RETN+ subsets, associated with leukocyte migration and inflammation, whereas healthy controls exhibited CD74+ monocytes linked to oxidative phosphorylation. Neutrophils in the patient were predominantly LTF+ and S100A12+, implicating inflammatory and immune regulatory pathways. These findings provide a detailed single-cell atlas of immune dysregulation post-jellyfish sting, highlighting the pivotal roles of MMP9+ monocytes and S100A12+ neutrophils in driving inflammation. This study offers potential therapeutic targets for mitigating severe immune responses in jellyfish envenomation.