Visualizing a lung neutrophil-platelet immunothrombosis cascade during sepsis in mice

Sepsis is an immune paradox where host defence is necessary for survival
but also contributes to organ damage and death. Using lung intravital
microscopy we defined an immunothrombosis cascade of neutrophil and
platelets in the microcirculation in response to E. coli sepsis.
Neutrophil cathelicidin localized neutrophils to E. coli and initiated
founder immunothrombi via formyl-peptide receptors. Immunothrombi captured
vascular bacteria and cathelicidin enabled antimicrobial activities in
platelets. Blocking cathelicidin prevented the immunothrombosis cascade
and attenuated early sepsis death but resulted in delayed death with
uncontrolled infection. LTB4 amplified the immunothrombi and inhibiting it
diminished detrimental immunothrombi while preserving host defense, thus
representing a discrete inflection point of sepsis disease progression.
Therefore, targeting the immunothrombi cascade can mitigate
immunopathology without suppressing host defence during sepsis.