Platelets determine the onset of innate and adaptive immune cell responses Schaubaecher J, Mittmann L, Uhl B, Reichel CA

Abstract

Neutrophils represent the first immune cells recruited to the site of injury or infection, followed by monocytes and, later on, lymphocytes. In addition to their fundamental role in hemostasis, platelets are increasingly recognized to serve as critical modulators of immune responses. Whereas interactions of platelets with myeloid leukocytes have been extensively studied, the functional relevance of these cellular blood components for the regulation of lymphocyte trafficking remains poorly understood. Employing multi‐channel in vivo microscopy on the mouse cremaster muscle, platelets were found to instantly accumulate in the venular microvasculature upon induction of inflammation right before neutrophils, monocytes, and lymphocytes, but are progressively released from the endothelium into the bloodstream after extravasation of myeloid leukocytes. In this context, platelets divergently control the trafficking of myeloid leukocytes and lymphocytes to inflamed tissue as assessed by multi‐channel flow cytometry analyses in a mouse peritonitis assay: Whereas depletion of platelets severely compromised the extravasation of neutrophils and classical monocytes, the recruitment of CD4+ lymphocytes, CD8+ lymphocytes, and B lymphocytes to the perivascular space was dramatically enhanced. Importantly, depletion of neutrophils in these experiments completely abolished responses of classical monocytes, but did not affect lymphocyte trafficking. In this context, activated platelets were found to upregulate surface expression of adhesion/signaling molecules facilitating interactions with neutrophils such as CD40 and CD40L as well as of factors interfering with lymphocyte activation including programmed death‐ligand 1 (PD‐L1), CD80, and CD86. Blockade of these latter immune checkpoint molecules significantly enhanced lymphocyte responses to the level of platelet‐depleted animals. Thus, our experimental data identify a previously unappreciated functional role of platelets as ‚decision makers' in the immune system that critically regulate the onset of innate and adaptive immune cell responses in inflammatory reactions.Support or Funding InformationThis study was supported by Deutsche Forschungsgemeinschaft (DFG), Sonderforschungs‐bereich (SFB) 914.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.