摘要：SummaryInflammation during neonatal brain infections leads to significant secondary sequelae such as hydrocephalus, which often follows neonatal sepsis in the developing world. In 100 African hydrocephalic infants we identified the biological pathways that account for this response. The dominant bacterial pathogen was aPaenibacillusspecies, with frequent cytomegalovirus co-infection. A proteogenomic strategy was employed to confirm host immune response toPaenibacillusand to define the interplay within the host immune response network. Immune activation emphasized neuroinflammation, oxidative stress reaction, and extracellular matrix organization. The innate immune system response included neutrophil activity, signaling via IL-4, IL-12, IL-13, interferon, and Jak/STAT pathways. Platelet-activating factors and factors involved with microbe recognition such as Class I MHC antigen-presenting complex were also increased. Evidence suggests that dysregulated neuroinflammation propagates inflammatory hydrocephalus, and these pathways are potential targets for adjunctive treatments to reduce the hazards of neuroinflammation and risk of hydrocephalus following neonatal sepsis.Graphical abstractDisplay OmittedHighlights•There is a characteristic immune response toPaenibacillusbrain infection•There is a characteristic immune response to CMV brain infection•The matching immune response validates pathogen genomic presence•The combined results support molecular infection causalityImmunology; Proteomics; Transcriptomics
