Meta-Analysis of Pulmonary Transcriptomes from Differently Primed Mice Identifies Molecular Signatures to Differentiate Immune Responses following Bordetella pertussis Challenge

Abstract

Respiratory infection with Bordetella pertussis leads to severe effects in the lungs. The resulting immunity and also immunization with pertussis vaccines protect against disease, but the induced type of immunity and longevity of the response are distinct. In this study the effects of priming, by either vaccination or infection, on a subsequent pathogen encounter were studied. To that end, three postchallenge transcriptome datasets of previously primed mice were combined and compared to the responses in unprimed control mice. In total, 205 genes showed different transcription activity. A coexpression network analysis assembled these genes into 27 clusters, combined into six groups with overlapping biological function. Local pulmonary immunity was only present in mice with infection-induced immunity. Complement-mediated responses were more prominent in mice immunized with an outer membrane vesicle pertussis vaccine than in mice that received a whole-cell pertussis vaccine. Additionally, 46 genes encoding for secreted proteins may serve as markers in blood for the degree of protection (Cxcl9, Gp2, and Pla2g2d), intensity of infection (Retnla, Saa3, Il6, and Il1b), or adaptive recall responses (Ighg, C1qb). The molecular signatures elucidated in this study contribute to better understanding of functional interactions in challenge-induced responses in relation to pertussis immunity.