Neutrophil serine proteases in antibacterial defense

Abstract

Neutrophil serine proteases (NSPs) are critical for the effective functioning of neutrophils and greatly contribute to immune protection against bacterial infections. Thanks to their broad substrate specificity, these chymotrypsin-like proteases trigger multiple reactions that are detrimental to bacterial survival such as direct bacterial killing, generation of antimicrobial peptides, inactivation of bacterial virulence factors and formation of neutrophil extracellular traps. Recently, the importance of NSPs in antibacterial defenses has been further underscored by discoveries of unique bacterial evasion strategies to combat these proteases. Bacteria can indirectly disarm NSPs by protecting bacterial substrates against NSP cleavage, but also produce inhibitory molecules that potently block NSPs. Here we review recent insights in the functional contribution of NSPs in host protection against bacterial infections and the elegant strategies that bacteria use to counteract these responses.

A structurally dynamic N-terminal region drives function of the staphylococcal peroxidase inhibitor (SPIN)

“…This results in the accumulation of high levels of antimicrobial enzymes in the phagosome, with concentrations of MPO estimated to approach 1 mM (25). Concentrations in this range have also been proposed for NSPs (7,(26)(27)(28), which render the maturing phagosomal compartment not only highly oxidizing, but exceptionally digestive in character. In light of this, the dynamicallystructured nature of the SPIN N-terminal region suggested that it might be susceptible to proteolysis.…”

Neutrophils and Bacterial Immune Evasion

“…In addition to AMP resistance, pathogenic bacteria have also developed mechanisms to evade targeting by other neutrophil granule constituents, including serine proteases such as neutrophil elastase, cathepsin G, proteinase 3, and neutrophil serine protease-4. The primary mechanisms of serine protease resistance used by bacterial pathogens are the modification of serine protease substrates and the production of serine protease inhibitors [43]. …”

Neutrophils and Immunity: From Bactericidal Action to Being Conquered

“…NSPs are critical for the effective functioning of neutrophils and greatly contribute to immune protection against bacterial infections [27]. NSPs are currently believed to have three functions.…”