Purpose of review: Neutrophil recruitment to sites of infection is a critical element of the innate immune response. In patients with sepsis, this response is dysregulated, with exuberant inflammation being followed by a state of profound immune suppression, including inhibition of neutrophil recruitment. This review examines mechanisms underlying suppression of neutrophil migration during sepsis.
Recent findings: Mechanisms governing neutrophil chemotactic function in sepsis are complex. Bacterial products, cytokines, and chemokines can modulate neutrophil migratory responses during sepsis via induction of cytoskeletal changes, inhibition of polymorphonuclear leukocyte (PMN)-endothelial cell interactions, and alterations in G protein-coupled receptor expression or signaling. Impaired chemotactic responses can occur as a result of dysregulated PMN Toll-like receptor signaling. Other recently identified inhibitory mechanisms include exposure to elevated temperatures, activation of the anti-inflammatory nuclear transcription factor peroxisome proliferator-activated receptor-gamma, and suppression of PMN-endothelial interactions due to nitric oxide and its metabolites. Finally, circulating microparticles released in sepsis exert important immunomodulatory effects on PMN adherence and transmigration.
Summary: Neutrophil recruitment is a coordinated process that is altered at multiple stages during sepsis, culminating in defective innate immunity and increased risk of infection in these patients. Defining mechanisms involved and strategies to interrupt these deleterious responses requires further investigation.