Role of neutrophils in innate immunity: a systems biology‐level approach

Abstract

The innate immune system is the first line of host defense against invading microorganisms. Polymorphonuclear leukocytes (PMNs or neutrophils) are the most abundant leukocyte in humans and essential to the innate immune response against invading pathogens. Compared to the acquired immune response, which requires time to develop and is dependent on previous interaction with specific microbes, the ability of neutrophils to kill microorganisms is immediate, non-specific, and not dependent on previous exposure to microorganisms. Historically, studies of PMN-pathogen interaction focused on the events leading to killing of microorganisms, such as recruitment/chemotaxis, transmigration, phagocytosis, and activation, whereas post-phagocytosis sequelae were infrequently considered. In addition, it was widely accepted that human neutrophils possessed limited capacity for new gene transcription and thus, relatively little biosynthetic capacity. This notion has changed dramatically within the past decade. Further, there is now more effort directed to understand the events occurring in PMNs after killing of microbes. Herein we review the systems biology-level approaches that have been used to gain an enhanced view of the role of neutrophils during host-pathogen interaction. We anticipate that these and future systems-level studies will ultimately will provide information critical to our understanding, treatment, and control of diseases caused by pathogenic microorganisms.

Neutrophil transcriptional profile changes during transit from bone marrow to sites of inflammation

“…1,2,10,11,[36][37][38] Although previous studies have shown that neutrophils can undergo rapid changes in gene expression upon bacterial challenge 3,4,12,13,39 or exposure to endotoxin, 3,4,10,40 it was previously unknown if and to what extent the neutrophil alters its transcriptome as it transits from the BM through the circulation and into sites of inflammation.…”

“…1 Their removal from the inflammatory site alongside elimination of deleterious stimulus is indispensable for maintaining host health. 1,2 It has been established that neutrophils are capable of changes in gene expression during inflammatory responses. 3 Subrahmanyam demonstrated that while neutrophils synthesize lower levels of protein and RNA, they are able to markedly change their gene expression following bacterial exposure.…”

“…9 Neutrophils undergo spontaneous apoptosis in order to maintain homeostasis, but also to regulate efficient resolution of inflammation. 2,10,11 Impaired clearance as well as delays in apoptotic events is critical to the progression of chronic inflammation. 3,12,13 A complex signaling interaction regulates neutrophil apoptosis and is initiated by two distinct pathways: the extrinsic pathway (death receptor pathway) and the intrinsic pathway (mitochondria pathway), where both pathways lead to activation of the characteristic caspase cascade 4,10 It is very likely that tight regulation of neutrophil apoptosis at different locations is a key feature of normal neutrophil function.…”

Surfactant Protein A (SP-A)-mediated Clearance of Staphylococcus aureus Involves Binding of SP-A to the Staphylococcal Adhesin Eap and the Macrophage Receptors SP-A Receptor 210 and Scavenger Receptor Class A

“…Previous studies have demonstrated that normal host responses involve recruitment of neutrophils that kill bacteria but undergo apoptosis in the process. Apoptotic neutrophils are then ingested by macrophages, limiting neutrophilic injury to host cells and tissues (58) (Fig. 8A).…”

Computational Systems Biology of Psoriasis: Are We Ready for the Age of Omics and Systems Biomarkers?

“…The production of inflammatory cytokines is induced by the activation of neutrophils (Sadik and Luster, 2012), which play an important role in the regulation of the innate immune response by recruiting chemokine gradients to the area of injury or infection (Kobayashi and DeLeo, 2009). CXCL8 is the main chemokine produced by neutrophils, activating them through CXCR2 in an autocrine loop (Soehnlein and Lindbom, 2010).…”