Abstract Severe bacterial pneumonia, a major cause of critical illness and death in adults, remains incompletely understood at the level of immune pathogenesis. This study provides the first single-cell perspective on immune responses in severe bacterial pneumonia, focusing on how these responses differ between survivors and non-survivors. Using single-cell RNA sequencing (scRNA-seq) and immune repertoire profiling (scBCR/TCR-seq), we analyzed peripheral blood mononuclear cells (PBMCs) from 40 patients and 32 healthy controls, identifying immune signatures that distinguish survivors from non-survivors. Our findings reveal a progressive collapse of both innate and adaptive immunity in non-survivors, characterized by disrupted intercellular communication, aborted monocyte maturation, defective innate effector functions, and maladaptive B/T cell responses. Specifically, non-survivors exhibit oligoclonal expansion of terminal plasma cells alongside impaired effector T cell function and concurrent hyperactivation of regulatory T cell (Treg) immunosuppressive activity. These results highlight the role of coordinated immune failure in disease progression and suggest potential immunomodulatory targets to improve outcomes. This abstract is funded by: None
Li et al. (Fri,) studied this question.