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Blood, 1 November 2007, Vol. 110, No. 9, pp. 3234-3244. Prepublished online as a Blood First Edition Paper on July 31, 2007; DOI 10.1182/blood-2007-03-079152. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-03-079152v1 110/9/3234    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Bhatnagar, S. Articles by Schorey, J. S. Search for Related Content PubMed PubMed Citation Articles by Bhatnagar, S. Articles by Schorey, J. S. Related Collections Immunobiology Phagocytes Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Exosomes released from macrophages infected with intracellular pathogens stimulate a proinflammatory response in vitro and in vivo Sanchita Bhatnagar1, Kazuhiko Shinagawa2, Francis J. Castellino2, and Jeffrey S. Schorey1 1 Department of Biological Sciences, Center for Global Health and Infectious Diseases, University of Notre Dame, IN; 2 Department of Chemistry and Biochemistry, W. M. Keck Center for Transgene Research, University of Notre Dame, IN Intracellular pathogens and the molecules they express have limited contact with the immune system. Here, we show that macrophages infected with intracellular pathogens Mycobacterium tuberculosis, M bovis BCG, Salmonella typhimurium, or Toxoplasma gondii release from cells small vesicles known as exosomes which contain pathogen-associated molecular patterns (PAMPs). These exosomes, when exposed to uninfected macrophages, stimulate a proinflammatory response in a Toll-like receptor– and myeloid differentiation factor 88–dependent manner. Further, exosomes isolated from the bronchoalveolar lavage fluid (BALF) of M bovis BCG–infected mice contain the mycobacteria components lipoarabinomannan and the 19-kDa lipoprotein and can stimulate TNF- production in naive macrophages. Moreover, exosomes isolated from M bovis BCG– and M tuberculosis–infected macrophages, when injected intranasally into mice, stimulate TNF- and IL-12 production as well as neutrophil and macrophage recruitment in the lung. These studies identify a previously unknown function for exosomes in promoting intercellular communication during an immune response to intracellular pathogens, and we hypothesize that extracellular release of exosomes containing PAMPs is an important mechanism of immune surveillance. 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Lerm Incorporation of Mycobacterium tuberculosis Lipoarabinomannan into Macrophage Membrane Rafts Is a Prerequisite for the Phagosomal Maturation Block Infect. Immun., July 1, 2008; 76(7): 2882 - 2887. [Abstract] [Full Text] [PDF] H. C. O'Neill and B. J. C. Quah Exosomes Secreted by Bacterially Infected Macrophages Are Proinflammatory Sci. Signal., February 12, 2008; 1(6): pe8 - pe8. [Abstract] [Full Text] [PDF]

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