A platelet-mediated system for shuttling blood-borne bacteria to CD8α+ dendritic cells depends on glycoprotein GPIb and complement C3

Nat Immunol. 2011 Oct 30;12(12):1194-201. doi: 10.1038/ni.2140.

Abstract

The acquisition of pathogen-derived antigen by dendritic cells (DCs) is a key event in the generation of cytotoxic CD8(+) T cell responses. In mice, the intracellular bacterium Listeria monocytogenes is directed from the blood to splenic CD8α(+) DCs. We report that L. monocytogenes rapidly associated with platelets in the bloodstream in a manner dependent on GPIb and complement C3. Platelet association targeted a small but immunologically important portion of L. monocytogenes to splenic CD8α(+) DCs, diverting bacteria from swift clearance by other, less immunogenic phagocytes. Thus, an effective balance is established between maintaining sterility of the circulation and induction of antibacterial immunity by DCs. Other gram-positive bacteria also were rapidly tagged by platelets, revealing a broadly active shuttling mechanism for systemic bacteria.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Platelets / metabolism
  • Blood Platelets / microbiology*
  • CD8 Antigens / metabolism*
  • CD8-Positive T-Lymphocytes / immunology
  • Complement C3 / metabolism*
  • Dendritic Cells / immunology*
  • Dendritic Cells / metabolism
  • Dendritic Cells / microbiology
  • Listeria monocytogenes / immunology*
  • Listeriosis / immunology
  • Listeriosis / microbiology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Platelet Aggregation / immunology
  • Platelet Glycoprotein GPIb-IX Complex / metabolism*
  • Platelet Membrane Glycoproteins / metabolism*
  • Spleen / immunology
  • Spleen / microbiology

Substances

  • CD8 Antigens
  • CD8alpha antigen
  • Complement C3
  • Platelet Glycoprotein GPIb-IX Complex
  • Platelet Membrane Glycoproteins