Lung Resident Memory T Cells Activated by Oral Vaccination Afford Comprehensive Protection against Pneumonic Yersinia pestis Infection

摘要

A growing body of evidence has shown that resident memory T (Trm) cells formed in tissue after mucosal infection or vaccination are crucial for counteracting reinfection by pathogens. However, whether lung T_(rm) cells activated by oral immunization with Yptbl(pYA5199) play a protective role against pneumonic plague remains unclear. In this study, we demonstrated that lung CD4~+ and CD8~+ T_(rm) cells significantly accumulated in the lungs of orally Yptbl(pYA5199)-vaccinated mice and dramatically expanded with elevated IL-17A, IFN-gamma, and/or TNF-alpha production after pulmonary Yersinia pestis infection and afforded significant protection. Short-term or long-term treatment of immunized mice with FTY720 did not affect lung T_(rm) cell formation and expansion or protection against pneumonic plague. Moreover, the intratracheal transfer of both lung CD4~+ and CD8~+ T_(rm) cells conferred comprehensive protection against pneumonic plague in naive recipient mice. Lung T_(rm) cell-mediated protection was dramatically abolished by the neutralization of both IFN-7 and IL-17A. Our findings reveal that lung T_(rm) cells can be activated via oral Yptbl(pYA5199) vaccination, and that IL-17A and IFN-7 production play an essential role in adaptive immunity against pulmonary Y. pestis infection. This study highlights an important new target for developing an effective pneumonic plague vaccine.