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

Admar Verschoor; Michael Neuenhahn; Alexander A. Navarini; Patricia Graef; Ann Plaumann; Amelie Seidlmeier; Bernhard Nieswandt; Steffen Massberg; Rolf M. Zinkernagel; Hans Hengartner; Dirk H. Busch

doi:10.1038/ni.2140

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

Admar Verschoor, Michael Neuenhahn, Alexander A. Navarini, Patricia Graef, Ann Plaumann, Amelie Seidlmeier, Bernhard Nieswandt, Steffen Massberg, Rolf M. Zinkernagel, Hans Hengartner, Dirk H. Busch^*

^*Corresponding author for this work

Institute of Systemic Inflamation Research

177 Citations (Scopus)

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.

Original language	English
Journal	Nature Immunology
Volume	12
Issue number	12
Pages (from-to)	1194-1201
Number of pages	8
ISSN	1529-2908
DOIs	https://doi.org/10.1038/ni.2140
Publication status	Published - 12.2011

Funding

We thank S. Gordon, P. Lachmann and H. Wagner for input; M. Botto (Imperial College, London) for C1qa−/−mice; M. Carroll (Harvard Medical School) for C3−/− and C4b−/− mice; C. Gerard (Harvard Medical School) for C3ar−/− mice; F. Petry (Johannes Gutenberg University of Mainz, Germany) for C1qa−/− mice; M. van der Linden (University Hospital Aachen, Germany) for Streptococcus strains; S. Feihl and V. Greifenberg for bacterial typing; L. Henkel, M. Schiemann and K. Wild for flow cytometry cell sorting; K. Mink, S. Vieweg and A. Wanisch for experimental assistance; and L. Layland for support preparing the manuscript. Supported by the German Research Foundation SFB 914 (TP-B4 to A.V. and D.H.B.) and SFB 576 (TP-A8 to D.H.B.), the Swiss National Foundation (3100AO-100779/2 and 3100AO-100068/2 to H.H. and R.M.Z.), the German Center for Infection Research (DZIF; D.H.B.) and the European Commission (Marie Curie Fellowship to A.V.).

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1038/ni.2140

Cite this

Verschoor, A., Neuenhahn, M., Navarini, A. A., Graef, P., Plaumann, A., Seidlmeier, A., Nieswandt, B., Massberg, S., Zinkernagel, R. M., Hengartner, H., & Busch, D. H. (2011). A platelet-mediated system for shuttling blood-borne bacteria to CD8α ⁺ dendritic cells depends on glycoprotein GPIb and complement C3. Nature Immunology, 12(12), 1194-1201. https://doi.org/10.1038/ni.2140

@article{cbec0ff40822456fa47bcb6b2c58bdec,

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

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.",

author = "Admar Verschoor and Michael Neuenhahn and Navarini, \{Alexander A.\} and Patricia Graef and Ann Plaumann and Amelie Seidlmeier and Bernhard Nieswandt and Steffen Massberg and Zinkernagel, \{Rolf M.\} and Hans Hengartner and Busch, \{Dirk H.\}",

note = "Funding Information: We thank S. Gordon, P. Lachmann and H. Wagner for input; M. Botto (Imperial College, London) for C1qa−/−mice; M. Carroll (Harvard Medical School) for C3−/− and C4b−/− mice; C. Gerard (Harvard Medical School) for C3ar−/− mice; F. Petry (Johannes Gutenberg University of Mainz, Germany) for C1qa−/− mice; M. van der Linden (University Hospital Aachen, Germany) for Streptococcus strains; S. Feihl and V. Greifenberg for bacterial typing; L. Henkel, M. Schiemann and K. Wild for flow cytometry cell sorting; K. Mink, S. Vieweg and A. Wanisch for experimental assistance; and L. Layland for support preparing the manuscript. Supported by the German Research Foundation SFB 914 (TP-B4 to A.V. and D.H.B.) and SFB 576 (TP-A8 to D.H.B.), the Swiss National Foundation (3100AO-100779/2 and 3100AO-100068/2 to H.H. and R.M.Z.), the German Center for Infection Research (DZIF; D.H.B.) and the European Commission (Marie Curie Fellowship to A.V.). Copyright: Copyright 2012 Elsevier B.V., All rights reserved.",

year = "2011",

month = dec,

doi = "10.1038/ni.2140",

language = "English",

volume = "12",

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journal = "Nature Immunology",

issn = "1529-2908",

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Verschoor, A, Neuenhahn, M, Navarini, AA, Graef, P, Plaumann, A, Seidlmeier, A, Nieswandt, B, Massberg, S, Zinkernagel, RM, Hengartner, H & Busch, DH 2011, 'A platelet-mediated system for shuttling blood-borne bacteria to CD8α ⁺ dendritic cells depends on glycoprotein GPIb and complement C3', Nature Immunology, vol. 12, no. 12, pp. 1194-1201. https://doi.org/10.1038/ni.2140

TY - JOUR

T1 - A platelet-mediated system for shuttling blood-borne bacteria to CD8α + dendritic cells depends on glycoprotein GPIb and complement C3

AU - Verschoor, Admar

AU - Neuenhahn, Michael

AU - Navarini, Alexander A.

AU - Graef, Patricia

AU - Plaumann, Ann

AU - Seidlmeier, Amelie

AU - Nieswandt, Bernhard

AU - Massberg, Steffen

AU - Zinkernagel, Rolf M.

AU - Hengartner, Hans

AU - Busch, Dirk H.

N1 - Funding Information: We thank S. Gordon, P. Lachmann and H. Wagner for input; M. Botto (Imperial College, London) for C1qa−/−mice; M. Carroll (Harvard Medical School) for C3−/− and C4b−/− mice; C. Gerard (Harvard Medical School) for C3ar−/− mice; F. Petry (Johannes Gutenberg University of Mainz, Germany) for C1qa−/− mice; M. van der Linden (University Hospital Aachen, Germany) for Streptococcus strains; S. Feihl and V. Greifenberg for bacterial typing; L. Henkel, M. Schiemann and K. Wild for flow cytometry cell sorting; K. Mink, S. Vieweg and A. Wanisch for experimental assistance; and L. Layland for support preparing the manuscript. Supported by the German Research Foundation SFB 914 (TP-B4 to A.V. and D.H.B.) and SFB 576 (TP-A8 to D.H.B.), the Swiss National Foundation (3100AO-100779/2 and 3100AO-100068/2 to H.H. and R.M.Z.), the German Center for Infection Research (DZIF; D.H.B.) and the European Commission (Marie Curie Fellowship to A.V.). Copyright: Copyright 2012 Elsevier B.V., All rights reserved.

PY - 2011/12

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N2 - 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.

AB - 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.

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U2 - 10.1038/ni.2140

DO - 10.1038/ni.2140

M3 - Journal articles

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AN - SCOPUS:81255208439

SN - 1529-2908

VL - 12

SP - 1194

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JO - Nature Immunology

JF - Nature Immunology

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