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Exosomes released from macrophages infected with intracellular pathogens stimulate a proinflammatory response in vitro and in vivo
- 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.
- Subjects :
- Salmonella typhimurium
Immunology
Inflammation
Biochemistry
Microbiology
Proinflammatory cytokine
Mice
Immune system
medicine
Animals
Tuberculosis
Cells, Cultured
Immunobiology
Mice, Knockout
Mice, Inbred BALB C
Salmonella Infections, Animal
Mycobacterium bovis
Lipoarabinomannan
biology
Macrophages
Secretory Vesicles
Intracellular parasite
Mycobacterium tuberculosis
Cell Biology
Hematology
biology.organism_classification
Microvesicles
Mice, Inbred C57BL
Toxoplasmosis, Animal
medicine.symptom
Toxoplasma
Intracellular
Subjects
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