Bergman, Molly A.Loomis, Wendy P.Mecsas, JoanStarnbach, MichaelIsberg, Ralph R.2010-11-082009Bergman, Molly A., Wendy P. Loomis, Joan Mecsas, Michael N. Starnbach, and Ralph R. Isberg. 2009. CD8+ T Cells Restrict Yersinia pseudotuberculosis infection: bypass of anti-phagocytosis by targeting antigen-presenting cells. PLoS Pathogens 5(9): e1000573.1553-7366http://nrs.harvard.edu/urn-3:HUL.InstRepos:4551385All Yersinia species target and bind to phagocytic cells, but uptake and destruction of bacteria are prevented by injection of anti-phagocytic Yop proteins into the host cell. Here we provide evidence that CD8+ T cells, which canonically eliminate intracellular pathogens, are important for restricting Yersinia, even though bacteria are primarily found in an extracellular locale during the course of disease. In a model of infection with attenuated Y. pseudotuberculosis, mice deficient for CD8+ T cells were more susceptible to infection than immunocompetent mice. Although exposure to attenuated Y. pseudotuberculosis generated TH1-type antibody responses and conferred protection against challenge with fully virulent bacteria, depletion of CD8+ T cells during challenge severely compromised protective immunity. Strikingly, mice lacking the T cell effector molecule perforin also succumbed to Y. pseudotuberculosis infection. Given that the function of perforin is to kill antigen-presenting cells, we reasoned that cell death marks bacteria-associated host cells for internalization by neighboring phagocytes, thus allowing ingestion and clearance of the attached bacteria. Supportive of this model, cytolytic T cell killing of Y. pseudotuberculosis–associated host cells results in engulfment by neighboring phagocytes of both bacteria and target cells, bypassing anti-phagocytosis. Our findings are consistent with a novel function for cell-mediated immune responses protecting against extracellular pathogens like Yersinia: perforin and CD8+ T cells are critical for hosts to overcome the anti-phagocytic action of Yops.en-USimmunologyimmunity to infectionsinfectious diseasesbacterial infectionsJournal Article2010-11-0810.1371/journal.ppat.1000573