TLR2-mediated neutrophil depletion exacerbates bacterial sepsis

Abstract

The host antimicrobial defense response is initiated by the innate immune system, the most ancient of the 2 limbs of the immune system. The innate immune system is activated as soon as a pathogen crosses the host external defense barriers, lasts for a few hours, and is aimed at the elimination of the invading microorganism. Detection of microbial pathogens is first carried out by sentinel cells [macrophages and dendritic cells (DCs)] located in tissues that are in direct contact with the host's natural environment or are rapidly recruited to the site of infection (neutrophils). This process involves coordinated actions of soluble and cellular molecules comprising components of the complement system, acute phase proteins such as the lipopolysaccharide-binding protein, extracellular or intracellular pattern-recognition types of molecules including the Toll-like receptors (TLR), the nucleotide-binding oligomerization domain-like receptors, RIG-I-like helicases, C-type lectin, and scavenger receptors. Recognition of invasive pathogens by immune cells relies on their capacity to detect microbial molecular motifs (for example, endotoxin, peptidoglycan subcomponents, lipopeptides, glucans, mannans, flagellin, and nucleic acids) via pattern-recognition receptors or molecules (1, 2).