Durable and controlled depletion of neutrophils in mice

Gael Boivin, Julien Faget, Pierre-Benoit Ancey, Aspasia Gkasti, Julie Mussard, Camilla Engblom, Christina Pfirschke, Caroline Contat, Justine Pascual, Jessica Vazquez, Nathalie Bendriss-Vermare, Christophe Caux, Marie-Catherine Vozenin, Mikael J. Pittet, Matthias Gunzer and Etienne Meylan ()
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Gael Boivin: Ecole Polytechnique Fédérale de Lausanne
Julien Faget: Ecole Polytechnique Fédérale de Lausanne
Pierre-Benoit Ancey: Ecole Polytechnique Fédérale de Lausanne
Aspasia Gkasti: Ecole Polytechnique Fédérale de Lausanne
Julie Mussard: University of Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon
Camilla Engblom: Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School
Christina Pfirschke: Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School
Caroline Contat: Ecole Polytechnique Fédérale de Lausanne
Justine Pascual: Ecole Polytechnique Fédérale de Lausanne
Jessica Vazquez: Ecole Polytechnique Fédérale de Lausanne
Nathalie Bendriss-Vermare: University of Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon
Christophe Caux: University of Lyon, Université Claude Bernard Lyon 1, INSERM 1052, CNRS 5286, Centre Léon Bérard, Cancer Research Center of Lyon
Marie-Catherine Vozenin: CHUV, Lausanne University Hospital and University of Lausanne
Mikael J. Pittet: Center for Systems Biology, Massachusetts General Hospital Research Institute and Harvard Medical School
Matthias Gunzer: University Hospital, University Duisburg–Essen
Etienne Meylan: Ecole Polytechnique Fédérale de Lausanne

Nature Communications, 2020, vol. 11, issue 1, 1-9

Abstract: Abstract Neutrophils are an essential part of the innate immune system. To study their importance, experimental studies often aim to deplete these cells, generally by injecting anti-Ly6G or anti-Gr1 antibodies. However, these approaches are only partially effective, transient or lack specificity. Here we report that neutrophils remaining after anti-Ly6G treatment are newly derived from the bone marrow, instead of depletion escapees. Mechanistically, newly generated, circulating neutrophils have lower Ly6G membrane expression, and consequently reduced targets for anti-Ly6G-mediated depletion. To overcome this limitation, we develop a double antibody-based depletion strategy that enhances neutrophil elimination by anti-Ly6G treatment. This approach achieves specific, durable and controlled reduction of neutrophils in vivo, and may be suitable for studying neutrophil function in experimental models.

Date: 2020
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DOI: 10.1038/s41467-020-16596-9

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