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Exosomes released from macrophages infected with intracellular pathogens stimulate a proinflammatory response in vitro and in vivo

Authors :
Sanchita Bhatnagar
Kazuhiko Shinagawa
Francis J. Castellino
Jeffrey S. Schorey
Source :
Blood. 110:3234-3244
Publication Year :
2007
Publisher :
American Society of Hematology, 2007.

Abstract

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-α production in naive macrophages. Moreover, exosomes isolated from M bovis BCG– and M tuberculosis–infected macrophages, when injected intranasally into mice, stimulate TNF-α 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.

Details

ISSN :
15280020 and 00064971
Volume :
110
Database :
OpenAIRE
Journal :
Blood
Accession number :
edsair.doi.dedup.....e2519082e2e1f543922453a24447670d
Full Text :
https://doi.org/10.1182/blood-2007-03-079152