Age-dependent role of type I interferon in the pathogenesis of Bordetella pertussis infection 3331

Abstract Description   Pertussis is an infectious disease that induces respiratory symptoms and persistent coughing in adults and children. Notably, pertussis can be particularly fatal for infants. Type I interferon (IFN) plays a multifaceted role in Bordetella pertussis infection; they are crucial for survival in infant mice but can heighten the inflammatory response in adult mice. Wild-type (WT) infant mice showed vulnerability to B. pertussis infection when inoculated on postnatal day 7 (P7). In contrast, WT mice survived the infection when inoculated at P10 and later. LysMcreIFNAR1fl/fl mice, which have myeloid-specific knockout of IFNAR1 (type I IFN receptor), succumbed to infection when inoculated at P10. P7 infant IFNAR1 SA mice with hyperactive IFNAR signaling had significantly improved survival rates after infection with B. pertussis. LysMcreIFNAR1fl/fl adult mice showed elevated levels of IFN lambda (IFN-λ) and lower lung inflammation compared to WT, indicating that myeloid cells may be the source of IFN-λ in these mice. IFNAR1 KO macrophages were able to induce IFN-λ following B. pertussis infection dependents on virulence protein pertussis toxin. Lysophosphatidic acid receptor 1 is a G protein-coupled receptor that regulates the secretion of IFN-λ dependent on PT in the IFNAR1 KO macrophages. Inhibition of STAT1 in B. pertussis-infected IFNAR1 KO macrophages inhibited IFN-λ secretion. Type I IFN-induced lung inflammation in adults but protective in infant mice to B.pertussis infection Funding Sources This work is supported by NIH grants R21AI168603 and R01AI141372. The 2024 AAI Careers in Immunology Fellowship is deeply acknowledged. Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)