PTX Instructs the Development of Lung-Resident Memory T Cells in Bordetella pertussis Infected Mice

Whooping cough is a severe, highly contagious disease of the human respiratory tract, caused by Bordetellapertussis. 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 establishment remain unknown. Comparing two B.pertussis strains expressing PTX (WT) or not (ΔPTX), we show that the toxin is required to generate both lung CD4⁺ and CD8⁺ Trm. Co-administering purified PTX with ΔPTX 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.