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 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.
Highlights
Whooping cough is a vaccine-preventable infectious disease caused by the gram-negative bacterium Bordetella pertussis responsible of approximately 100,000 child deaths each year worldwide [1]
Ptx genes are found in closely related Bordetella species, pertussis toxin (PTX) is exclusively produced by B. pertussis [3]
We aimed at deciphering the impact of pertussis toxin (PTX) on the immune response during B. pertussis infection by comparing the T cell-mediated immunity triggered by a PTX producing strain (WT) to that of a PTX-deficient, isogenic strain
Summary
Whooping cough (pertussis) is a vaccine-preventable infectious disease caused by the gram-negative bacterium Bordetella pertussis responsible of approximately 100,000 child deaths each year worldwide [1]. Pertussis toxin (PTX) has been shown to contribute primarily to the severity of the disease [2]. PTX is a member of the ADPribosylating toxin family leading to accumulation of cAMP in target cells [4]. PTX activates innate immune responses and modulates adaptive immune responses towards a mixed Th1/Th17 balance [6,7,8]. For all these reasons, pertussis toxin (PTX) is the major antigen for establishing an immune response against this bacterium and the main and common component of all current pertussis vaccines
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