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WIREs Syst Biol Med
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Neutrophils in innate immunity and systems biology‐level approaches

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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, nonspecific, 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 postphagocytosis 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 20 years. Further, there is now more effort directed to understand the events occurring in PMNs after killing of microbes. Herein, we give an updated review of the systems biology‐level approaches that have been used to gain an enhanced view of the role of neutrophils during host‐pathogen interaction and neutrophil‐mediated diseases. We anticipate that these and future systems‐level studies will continue to provide information important for understanding, treatment, and control of diseases caused by pathogenic microorganisms. This article is categorized under: Physiology > Organismal Responses to Environment Physiology > Mammalian Physiology in Health and Disease Biological Mechanisms > Cell Fates
Overview of neutrophil functions / processes that have been investigated using proteomics, transcriptomics, genomics and lipidomics. PICD, phagocytosis‐induced cell death. See text for details
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A schematic that illustrates possible outcomes of microbe‐neutrophil interaction. See text for details
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Neutrophil apoptosis. Human neutrophils were isolated from venous blood and then processed for transmission electron microscopy or stained with Wright‐Giemsa (inset) after purification (0 hr) or 24 hr in culture
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Neutrophil phagocytosis and microbicidal process. Panel (a) illustrates binding and phagocytosis of a microbe opsonized with antibody or serum complement. Phagocytosis triggers production of superoxide (O2•–) from which other secondarily derived ROS are formed, including hydrogen peroxide (H2O2) and hypochlorous acid (HOCl). Panel (b) is a transmission electron micrograph of a human neutrophil that has phagocytosed numerous Staphylococcus aureus (Microbe)
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Physiology > Mammalian Physiology in Health and Disease
Physiology > Organismal Responses to Environment
Biological Mechanisms > Cell Fates

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