Search

Human polymorphonuclear leukocytes (PMNs) are the first line of defense against invading microorganisms. Although most invading bacteria are eliminated by PMNs, some have evolved complex strategies to prevent normal PMN function. This review focuses on the interaction of human PMNs with Streptococcus pyogenes as a paradigm for successful pathogen evasion mechanisms.

Invasive Staphylococcus aureus (S. aureus) disease is associated with neutrophil activity and pro-inflammatory cytokine expression, including interferon-gamma (IFNγ). Using a mouse model of S. aureus peritonitis, we identify neutrophils as the predominant source of IFNγ and link this induction with the SaeR/S two-component gene regulatory system. Relative to wild-type (BALB/c) mice, IFNγ-deficient mice demonstrated increased bacterial clearance and reduced cellular cytotoxicity following intraperitoneal challenge with S. aureus. Interestingly, bacterial burden and cytotoxicity were similar in BALB/c and IFNγ-deficient mice when infected with an isogenic saeR/S mutant strain. These findings suggest saeR/S-mediated neutrophil-derived IFNγ diminishes innate antibacterial mechanisms against S. aureus.

Human polymorphonuclear leukocytes (PMNs) are the first line of defense against invading microorganisms and contribute significantly to inflammation. Recent evidence suggests that resolution of neutrophil-mediated inflammation is facilitated by an apoptosis differentiation program, a final stage of transcriptionally regulated PMN maturation that is accelerated significantly by phagocytosis.