The C5a-C5aR1 complement axis is essential for neutrophil recruitment to draining lymph nodes via high endothelial venules in cutaneous leishmaniasis
Borja Prat-Luri,
Christopher Neal,
Katiuska Passelli,
Emma Ganga,
Jonas Amore,
Luan Firmino-Cruz,
Tatiana V. Petrova,
Andreas J. Müller,
Fabienne Tacchini-Cottier
Affiliations
Borja Prat-Luri
Department of Immunobiology, WHO Collaborative Center for Research and Training in Immunology, University of Lausanne, Epalinges, Switzerland; Corresponding author
Christopher Neal
Department of Immunobiology, WHO Collaborative Center for Research and Training in Immunology, University of Lausanne, Epalinges, Switzerland
Katiuska Passelli
Department of Immunobiology, WHO Collaborative Center for Research and Training in Immunology, University of Lausanne, Epalinges, Switzerland
Emma Ganga
Department of Immunobiology, WHO Collaborative Center for Research and Training in Immunology, University of Lausanne, Epalinges, Switzerland
Jonas Amore
Otto-von-Guericke-University Magdeburg and Helmholtz Centre for Infection Research Braunschweig, Magdeburg, Germany
Luan Firmino-Cruz
Department of Immunobiology, WHO Collaborative Center for Research and Training in Immunology, University of Lausanne, Epalinges, Switzerland
Tatiana V. Petrova
Department of Oncology, University of Lausanne, Epalinges, Switzerland; Ludwig Institute for Cancer Research Lausanne, Epalinges, Switzerland
Andreas J. Müller
Otto-von-Guericke-University Magdeburg and Helmholtz Centre for Infection Research Braunschweig, Magdeburg, Germany
Fabienne Tacchini-Cottier
Department of Immunobiology, WHO Collaborative Center for Research and Training in Immunology, University of Lausanne, Epalinges, Switzerland; Corresponding author
Summary: Neutrophils are specialized innate immune cells known for their ability to fight pathogens. However, the mechanisms of neutrophil trafficking to lymph nodes are not fully clear. Using a murine model of dermal infection with Leishmania parasites, we observe a transient neutrophil influx in draining lymph nodes despite sustained recruitment to the infection site. Cell-tracking experiments, together with intravital two-photon microscopy, indicate that neutrophil recruitment to draining lymph nodes occurs minimally through lymphatics from the infected dermis, but mostly through blood vessels via high endothelial venules. Mechanistically, neutrophils do not respond to IL-1β or macrophage-derived molecules. Instead, they are guided by the C5a-C5aR1 axis, using L-selectin and integrins, to extravasate into the draining lymph node parenchyma. We also report that C5, the C5a precursor, is locally produced in the draining lymph node by lymphatic endothelial cells. Our data establish and detail organ-specific mechanisms of neutrophil trafficking.
