A platelet-mediated system for shuttling blood-borne bacteria to CD8α+ dendritic cells depends on glycoprotein GPIb and complement C3.
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.
Institute for Medical Microbiology, Immunology and Hygiene, and Focus Group, Clinical Cell Processing and Purification, Technische Universität München, Munich, Germany. admar.verschoor@mikrobio.med.tum.de
Admar
A
Verschoor
Michael
M
Neuenhahn
Alexander A
AA
Navarini
Patricia
P
Graef
Ann
A
Plaumann
Amelie
A
Seidlmeier
Bernhard
B
Nieswandt
Steffen
S
Massberg
Rolf M
RM
Zinkernagel
Hans
H
Hengartner
Dirk H
DH
Busch
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism / Q000382:microbiology*; D016827:CD8 Antigens / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003176:Complement C3 / Q000378:metabolism*; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D008089:Listeria monocytogenes / Q000276:immunology*; D008088:Listeriosis / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010974:Platelet Aggregation / Q000276:immunology; D019038:Platelet Glycoprotein GPIb-IX Complex / Q000378:metabolism*; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism*; D013154:Spleen / Q000276:immunology / Q000382:microbiology
D016827:CD8 Antigens; C431698:CD8alpha antigen; D003176:Complement C3; D019038:Platelet Glycoprotein GPIb-IX Complex; D010980:Platelet Membrane Glycoproteins