Necroptotic Cell Death Promotes Adaptive Immunity Against Colonizing Pneumococci.

ABSTRACT: Pore-forming toxin (PFT) induced necroptosis exacerbates pulmonary injury during bacterial pneumonia. However, its role during asymptomatic nasopharyngeal colonization and toward the development of protective immunity was unknown. Using a mouse model of Streptococcus pneumoniae (Spn) asymptomatic colonization, we determined that nasopharyngeal epithelial cells (nEC) died of pneumolysin (Ply)-dependent necroptosis. Mice deficient in MLKL, the necroptosis effector, or challenged with Ply-deficient Spn showed less nEC sloughing, increased neutrophil infiltration, and altered IL-1α, IL-33, CXCL2, IL-17, and IL-6 levels in nasal lavage fluid (NALF). Activated MLKL correlated with increased presence of CD11c⁺ antigen presenting cells in Spn-associated submu

SUBMITTER: Riegler AN 

PROVIDER: S-EPMC6459137 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature