| First Author | Riegler AN | Year | 2019 |
| Journal | Front Immunol | Volume | 10 |
| Pages | 615 | PubMed ID | 31019504 |
| Mgi Jnum | J:284320 | Mgi Id | MGI:6380809 |
| Doi | 10.3389/fimmu.2019.00615 | Citation | Riegler AN, et al. (2019) Necroptotic Cell Death Promotes Adaptive Immunity Against Colonizing Pneumococci. Front Immunol 10:615 |
| abstractText | 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-1alpha, 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 submucosa. Colonized MLKL KO mice and wildtype mice colonized with Ply-deficient Spn produced less antibody against the bacterial surface protein PspA, were delayed in bacterial clearance, and were more susceptible to a lethal secondary Spn challenge. We conclude that PFT-induced necroptosis is instrumental in the natural development of protective immunity against opportunistic PFT-producing bacterial pathogens. |
