dc.contributor.author | Bergman, Molly A. | |
dc.contributor.author | Loomis, Wendy P. | |
dc.contributor.author | Mecsas, Joan | |
dc.contributor.author | Starnbach, Michael N. | |
dc.contributor.author | Isberg, Ralph R. | |
dc.date.accessioned | 2010-11-08T16:58:02Z | |
dc.date.issued | 2009 | |
dc.identifier.citation | Bergman, 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. | en_US |
dc.identifier.issn | 1553-7366 | en_US |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:4551385 | |
dc.description.abstract | All 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_US |
dc.description.sponsorship | Molecular and Cellular Biology | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Public Library of Science | en_US |
dc.relation.isversionof | http://dx.doi.org/10.1371/journal.ppat.1000573 | en_US |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2731216/pdf/ | en_US |
dash.license | OAP | |
dc.subject | immunology | en_US |
dc.subject | immunity to infections | en_US |
dc.subject | infectious diseases | en_US |
dc.subject | bacterial infections | en_US |
dc.title | CD8+ T Cells Restrict Yersinia pseudotuberculosis Infection: Bypass of Anti-Phagocytosis by Targeting Antigen-Presenting Cells | en_US |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en_US |
dc.relation.journal | PLoS Pathogens | en_US |
dash.depositing.author | Starnbach, Michael N. | |
dc.date.available | 2010-11-08T16:58:02Z | |
dc.identifier.doi | 10.1371/journal.ppat.1000573 | * |
dash.contributor.affiliated | Starnbach, Michael | |