Toll-like receptors elicit different recruitment kinetics of monocytes and neutrophils in mouse acute inflammation.

Abstract

Leukocyte recruitment is an important process in combating pathogens. The largest class of circulating leukocytes are neutrophils, which rapidly invade inflamed tissue, followed by inflammatory Ly6C+ monocytes. Ly6Clow monocytes patrol the endothelial wall routinely in the steady state. We recently reported early luminal recruitment of Ly6Clow monocytes, which preceded and orchestrated neutrophil arrival and extravasation in response to TLR7/8-mediated vascular inflammation. Here we dissected the kinetics of recruitment of monocytes and neutrophils and examined the dynamics of Ly6Clow monocytes in response to several other Toll-like receptor (TLR) agonists, using intravital confocal microscopy. We observed two types of kinetics in mesenteric veins. TLR2, TLR5 and TLR9 agonists caused early monocyte and neutrophil influx whereas TLR3 and TLR4 agonists rapidly recruited neutrophils and caused Ly6Clow monocytes to arrive at low levels later on. All TLR agonists, except TLR9, led Ly6Clow monocytes to meticulously patrol the vascular wall. Finally, these monocytes released pro-inflammatory cytokines and chemokines implicated in neutrophil recruitment in response to TLR2, TLR4, and TLR9 stimulation but not to TLR3 and TLR5 agonists. These results refine our understanding of the early events in the leukocyte recruitment cascade, including the patrolling behavior of Ly6Clow monocytes, in TLR-mediated acute vascular inflammation.