neutrophil-mediated killing of gram-positive bacterium

Definition

Target type: biologicalprocess

The directed killing of a gram-positive bacterium by a neutrophil. [GOC:add, ISBN:0781765196]

Neutrophils, a type of white blood cell, are essential in the innate immune response to gram-positive bacteria. They employ a multi-faceted arsenal to kill these pathogens, utilizing both oxidative and non-oxidative mechanisms.

**1. Recognition and Attachment:** Neutrophils recognize gram-positive bacteria through pattern recognition receptors (PRRs) on their surface, such as Toll-like receptors (TLRs) and complement receptors. These receptors bind to pathogen-associated molecular patterns (PAMPs) specific to gram-positive bacteria, including lipoteichoic acid (LTA) and peptidoglycan. This recognition triggers neutrophil activation and adhesion to the bacteria.

**2. Phagocytosis:** Activated neutrophils engulf the gram-positive bacterium through a process called phagocytosis. The cell membrane of the neutrophil surrounds the bacterium, internalizing it into a phagosome.

**3. Phagosome-Lysosome Fusion:** The phagosome then fuses with lysosomes, intracellular organelles containing a cocktail of degradative enzymes and antimicrobial agents. These include:

* **Oxidative Mechanisms:**
* **Reactive Oxygen Species (ROS):** The NADPH oxidase enzyme complex within the neutrophil generates superoxide radicals (O2-), which are further converted into other reactive oxygen species like hydrogen peroxide (H2O2) and hypochlorous acid (HOCl). These ROS damage bacterial cell membranes and proteins, leading to bacterial death.
* **Myeloperoxidase (MPO):** This enzyme uses hydrogen peroxide to generate hypochlorous acid, a highly reactive and potent antimicrobial agent that further damages bacterial components.

* **Non-Oxidative Mechanisms:**
* **Lysosomal Enzymes:** Lysosomes release a variety of enzymes, including proteases, lipases, and nucleases, that degrade bacterial proteins, lipids, and nucleic acids.
* **Defensins:** These small cationic peptides disrupt bacterial cell membranes, leading to cell lysis.
* **Neutrophil Extracellular Traps (NETs):** In response to certain pathogens, neutrophils release a web of DNA fibers decorated with antimicrobial proteins, like histones and elastase, which trap and kill bacteria.

**4. Killing and Degradation:** The combination of oxidative and non-oxidative mechanisms within the phagolysosome results in the destruction and degradation of the engulfed gram-positive bacterium.

**5. Inflammatory Response:** Neutrophils also release pro-inflammatory cytokines, such as TNF-α and IL-1β, that amplify the immune response and recruit other immune cells to the site of infection.

**Note:** The specific mechanisms and effectiveness of neutrophil-mediated killing can vary depending on the bacterial species and the host's immune status.'
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Compounds (16)