Modeling neonatal immune response to B. pertussis identifies early B cell activation and differentiation.

Pertussis is typically more severe in neonates and young infants, with fulminant forms possibly linked to age-specific systemic immune responses. However, the early events that shape the development of the immune response in neonates are poorly understood, mainly due to limited sample access and the absence of human ex vivo infection models. Here, multi-omic profiling of an ex vivo whole-blood infection model was used to investigate systemic immune responses to Bordetella pertussis. We observed a stronger pro-inflammatory immune response in cord blood (CB) compared to adult blood (AB), marked by a hyperinflammatory cytokine signature and an early loss of myeloid-derived suppressor cells. B cell remodeling was observed in both blood types, characterized by an increased fraction of CD25 + B lymphocytes exhibiting an activated transitional phenotype, with upregulated expression of activation markers, chemokines and immunosuppressors. Transcriptomic analysis of whole blood revealed a skewed immune response favoring innate immune cell activation in CB. Our findings shed light on early immune responses to B. pertussis, paving the way for further exploration of immune pathways in the pathogenesis of this major public health threat.