PTX instructs the development of lung-resident memory T cells in bordetella pertussis infected mice

Abstract

Whooping cough is a severe, highly contagious disease of the human respiratory tract, caused by Bordetella pertussis. The pathogenicity requires several virulence factors, including pertussis toxin (PTX), a key component of current available vaccines. Current vaccines do not induce mucosal immunity. Tissue-resident memory T cells (Trm) are among the first lines of defense against invading pathogens and are involved in long-term protection. However, the factors involved in Trm estab-lishment remain unknown. Comparing two B. pertussis strains expressing PTX (WT) or not (∆PTX), we show that the toxin is required to generate both lung CD4+ and CD8+ Trm. Co-administering purified PTX with ∆PTX is sufficient to generate these Trm subsets. Importantly, adoptive transfer of lung CD4+ or CD8+ Trm conferred protection against B. pertussis in naïve mice. Taken together, our data demonstrate for the first time a critical role for PTX in the induction of mucosal long-term protection against B. pertussis.