Prof. Kingston Mills - Local T cells and their subversion in protective immunity to infection in the respiratory tract
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Respiratoryinfection with Bordetella pertussis causeswhooping cough. The infection is controlled by innate immune responses, but completebacterial clearance from the respiratory tract and protection againstre-infection is mediated largely by Th1 and Th17 cells. However the bacteriahas evolved sophisticated immune subversion strategies to subvert theseresponses Antigen-specificregulatory T (Treg) cells that secrete IL-10 are induced in the respiratorytract during B. pertussis infectionand suppress protective T cell responses. Pertussis disease can be prevented in childrenby immunization with acellular pertussis (aP) vaccines. However, aP vaccinesfail to prevent nasal colonization and transmission of B. pertussis and may enhance infection in the nasal mucosae. Thismay be due to activation of immune checkpoints or Treg cells. aP vaccine failto induce Th1or Th17 cells or respiratory tissueresident memory T (TRM) cells that maintain long term immunity inthe respiratory tract. We found that blocking IL-10 during immunizationrestores the induction of Th1 and Th17 responses and enhances efficacy of an aPvaccine. Furthermore, we have demonstrated that immunization with an aP vaccineformulated with a novel adjuvant combination, comprising TLR2 and STINGagonists, induces Th1- and Th17-type TRM cells in the lung and nasaltissue, especially when delivered by nasal route, and this confers long-term protectionagainst nasal colonization as well as lung infection.
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