Suppression of mucosal Th17 memory responses by acellular pertussis vaccines enhances nasal Bordetella pertussis carriage.

ABSTRACT: Pertussis has made a spectacular rebound in countries that have switched from whole-cell (wPV) to acellular pertussis vaccines (aPV). Here, we show that, unlike wPV, aPV, while protective against lung colonization by Bordetella pertussis (Bp), did not protect BALB/c mice from nasal colonization, but instead substantially prolonged nasal carriage. aPV prevented the natural induction of nasal interleukin-17 (IL-17)-producing and interferon-? (IFN-?)-producing CD103⁺ CD44⁺ CD69⁺ CD4⁺-resident memory T (T_RM) cells. IL-17-deficient, but not IFN-?-deficient, mice failed to clear nasal Bp, indicating a key role of IL-17⁺ T_RM cells in the control of nasal infection. These cells appeared essential for neutrophil recruitment, crucial for clearance of Bp tightly bound to the nasal epithelium. Transfer of IL-17⁺ T_RM cells from Bp-infected mice to IL-17-deficient mice resulted in neutrophil recruitment and protection against nasal colonization. Thus, aPV may have augmented the Bp reservoir by inhibiting natural T_RM cell induction and neutrophil recruitment, thereby contributing to the pertussis resurgence.

SUBMITTER: Dubois V 

PROVIDER: S-EPMC7794405 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature