Neutrophils have traditionally been thought of as simple foot soldiers of the innate immune system with a restricted set of pro-inflammatory functions. More recently, it has become apparent that neutrophils are, in fact, complex cells capable of a vast array of specialized functions. Although neutrophils are undoubtedly major effectors of acute inflammation, several lines of evidence indicate that they also contribute to chronic inflammatory conditions and adaptive immune responses. Here, we discuss the key features of the life of a neutrophil, from its release from bone marrow to its death. We discuss the possible existence of different neutrophil subsets and their putative anti-inflammatory roles. We focus on how neutrophils are recruited to infected or injured tissues and describe differences in neutrophil recruitment between different tissues. Finally, we explain the mechanisms that are used by neutrophils to promote protective or pathological immune responses at different sites.

Neutrophil recruitment and function in health and inflammation

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.

/pdf/the-multifaceted-functions-of-neutrophils-5bl9p6i8k4.pdf

The Multifaceted Functions of Neutrophils

Neutrophils are the most abundant leukocytes in the circulation, and have been regarded as first line of defense in the innate arm of the immune system. They capture and destroy invading microorganisms, through phagocytosis and intracellular degradation, release of granules, and formation of neutrophil extracellular traps after detecting pathogens. Neutrophils also participate as mediators of inflammation. The classical view for these leukocytes is that neutrophils constitute a homogenous population of terminally differentiated cells with a unique function. However, evidence accumulated in recent years, has revealed that neutrophils present a large phenotypic heterogeneity and functional versatility, which place neutrophils as important modulators of both inflammation and immune responses. Indeed, the roles played by neutrophils in homeostatic conditions as well as in pathological inflammation and immune processes are the focus of a renovated interest in neutrophil biology. In this review, I present the concept of neutrophil phenotypic and functional heterogeneity and describe several neutrophil subpopulations reported to date. I also discuss the role these subpopulations seem to play in homeostasis and disease.

/pdf/neutrophil-a-cell-with-many-roles-in-inflammation-or-several-3urnastgfv.pdf

Neutrophil: A Cell with Many Roles in Inflammation or Several Cell Types?

In this Review we discuss data demonstrating recently recognized aspects of neutrophil homeostasis in the steady state, granulopoiesis in 'emergency' conditions and interactions of neutrophils with the adaptive immune system. We explore in vivo observations of the recruitment of neutrophils from blood to tissues in models of blood-borne infections versus bacterial invasion through epithelial linings. We examine data on novel aspects of the activation of NADPH oxidase and the heterogeneity of phagosomes and, finally, consider the importance of two neutrophil-derived biological agents: neutrophil extracellular traps and ectosomes.

Neutrophils at work

Protective responses to microorganisms involve the nonspecific but rapid defence mechanisms of the innate immune system, followed by the specific but slow defence mechanisms of the adaptive immune system. Located as sentinels at the interface between the circulation and lymphoid tissue, splenic marginal zone B cells rapidly respond to blood-borne antigens by adopting 'crossover' defensive strategies that blur the conventional boundaries of innate and adaptive immunity. This Review discusses how marginal zone B cells function as innate-like lymphocytes that mount rapid antibody responses to both T cell-dependent and T cell-independent antigens. These responses require the integration of activation signals from germline-encoded and somatically recombined receptors for microorganisms with helper signals from effector cells of the innate and adaptive immune systems.

/pdf/marginal-zone-b-cells-virtues-of-innate-like-antibody-2kthu45jl6.pdf

Marginal zone B cells: virtues of innate-like antibody-producing lymphocytes

Follicular T cells provide help to B cells to elicit antibody responses. Cerutti and colleagues show that neutrophils provide help to marginal-zone B cells that produce T cell–independent antibodies.

/pdf/b-cell-helper-neutrophils-stimulate-the-diversification-and-1k3r0dr3a6.pdf

Bing-Yang He

Papers

B cell–helper neutrophils stimulate the diversification and production of immunoglobulin in the marginal zone of the spleen