The Multifaceted Functions of Neutrophils

Abstract

Neutrophils and neutrophil-like cells are the major pathogen-fighting immune cells in organisms ranging from slime molds to mammals. Central to their function is their ability to be recruited to sites of infection, to recognize and phagocytose microbes, and then to kill pathogens through a combination of cytotoxic mechanisms. These include the production of reactive oxygen species, the release of antimicrobial peptides, and the recently discovered expulsion of their nuclear contents to form neutrophil extracellular traps. Here we discuss these primordial neutrophil functions, which also play key roles in tissue injury, by providing details of neutrophil cytotoxic functions and congenital disorders of neutrophils. In addition, we present more recent evidence that interactions between neutrophils and adaptive immune cells establish a feed-forward mechanism that amplifies pathologic inflammation. These newly appreciated contributions of neutrophils are described in the setting of several inflammatory and autoimmune diseases.

Nonredundant protective properties of FPR2/ALX in polymicrobial murine sepsis

“…Indeed, high levels of cytokines quantified in Fpr2/3 −/− mice could underlie organ dysfunction: There are indications that unabated circulating cytokines are predictive of early mortality in sepsis (38). Some of them, like TNFα and IL-1β, can exert a direct effect through increased expression of inducible NO synthase (39,40). In any case, the augmented myocardial injury determined by Fpr2/3 absence was functional, as evident with poor systolic pressure and pulse.…”

Neutrophil-Epithelial Interactions

“…Compared with the short paracellular space between endothelial cells (2 to 4 mm), the distance across the paracellular or basolateral space between epithelial cells is considerably longer, up to 20 mm. 6 It is thus reasonable to envision multiple adhesive interactions that are necessary for a neutrophil to translocate across the epithelium. Some of the complex molecular interactions that mediate neutrophil migration across the epithelium are highlighted in the paragraphs below.…”

Neutrophils induce proangiogenic T cells with a regulatory phenotype in pregnancy

“…Neutrophils, classically considered short-lived cells, provide a first line of defense during infection to help ensure tissue restitution to physiology (8,9). Emerging evidence indicates that neutrophils also may regulate specific processes typical of adaptive immune responses (10), including antibody production from B cells (11), T-cell suppression (12), and antigen presentation by dendritic cells (13).…”