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

Sanchita Bhatnagar1, Kazuhiko Shinagawa, Francis J Castellino

  • 1Department of Biological Sciences, Center for Global Health and Infectious Diseases, University of Notre Dame, 130 Galvin Life Science Center, Notre Dame, IN 46556, USA.

Blood
|August 2, 2007
PubMed

Insights

Macrophages infected with intracellular pathogens release exosomes containing pathogen-associated molecular patterns (PAMPs). These exosomes alert other immune cells, promoting inflammation and enhancing immune surveillance against infections.

Area of Science:

  • Immunology
  • Cell Biology
  • Microbiology

Background:

  • Intracellular pathogens have limited interaction with the host immune system.
  • Macrophages are key immune cells involved in combating pathogens.

Purpose of the Study:

  • To investigate the role of exosomes in immune response to intracellular pathogens.
  • To determine if exosomes released by infected macrophages contain pathogen-associated molecular patterns (PAMPs).

Main Methods:

  • Infection of macrophages with Mycobacterium tuberculosis, M bovis BCG, Salmonella typhimurium, or Toxoplasma gondii.
  • Isolation and analysis of exosomes from infected cells and bronchoalveolar lavage fluid (BALF).
  • Stimulation of naive macrophages with exosomes and assessment of immune responses in vivo and in vitro.

Main Results:

  • Infected macrophages release exosomes containing PAMPs.
  • Exosomes stimulate proinflammatory responses in naive macrophages via Toll-like receptor and MyD88 pathways.
  • Exosomes from infected mice BALF induce TNF-alpha production.
  • Intranasal administration of exosomes promotes lung immune cell recruitment and cytokine production.

Conclusions:

  • Exosomes play a novel role in intercellular communication during immune responses to intracellular pathogens.
  • Extracellular release of exosomes carrying PAMPs is a potential mechanism for immune surveillance.

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