neutrophil-mediated killing of gram-negative bacterium

Definition

Target type: biologicalprocess

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

Neutrophils are a type of white blood cell that play a critical role in the innate immune response to bacterial infections. They are highly effective at killing gram-negative bacteria through a multi-step process that involves chemotaxis, phagocytosis, and the release of cytotoxic molecules.

**1. Chemotaxis:** Neutrophils are attracted to the site of infection by chemoattractants released by the bacteria themselves, as well as by other immune cells already present at the site. These chemoattractants include bacterial products like lipopolysaccharide (LPS), formyl peptides, and chemokines produced by resident macrophages and other cells.

**2. Phagocytosis:** Once neutrophils reach the infection site, they recognize and engulf gram-negative bacteria. This process is initiated by the binding of bacterial surface molecules, such as LPS, to receptors on the neutrophil surface. These receptors include TLR4, which recognizes LPS, and Fc receptors, which bind to antibodies that may have coated the bacteria. Following binding, the neutrophil membrane invaginates around the bacterium, forming a phagosome.

**3. Formation of the Phagolysosome:** The phagosome containing the bacterium fuses with lysosomes, which are intracellular organelles filled with enzymes and other antimicrobial agents. This fusion results in the formation of a phagolysosome, where the destruction of the bacterium takes place.

**4. Oxidative Burst and Release of Reactive Oxygen Species (ROS):** Inside the phagolysosome, neutrophils generate a burst of reactive oxygen species (ROS), including superoxide anions, hydrogen peroxide, and hydroxyl radicals. These highly reactive molecules are toxic to bacterial cells and contribute significantly to their killing. NADPH oxidase, an enzyme complex found in neutrophil membranes, plays a crucial role in generating superoxide anions, the precursor of other ROS.

**5. Release of Antimicrobial Enzymes and Peptides:** Neutrophils also release a variety of antimicrobial enzymes and peptides into the phagolysosome, further contributing to bacterial destruction. These include:

* **Lysozyme:** This enzyme hydrolyzes peptidoglycan, a major component of the bacterial cell wall, leading to cell lysis.
* **Myeloperoxidase (MPO):** MPO uses hydrogen peroxide to generate hypochlorous acid (HOCl), a potent oxidant that damages bacterial membranes and other essential molecules.
* **Defensins:** These cationic peptides disrupt bacterial cell membranes, causing leakage and death.
* **Proteases:** These enzymes degrade bacterial proteins, interfering with essential functions.

**6. Neutrophil Extracellular Traps (NETs):** Neutrophils can also release neutrophil extracellular traps (NETs), which are web-like structures composed of DNA, histones, and antimicrobial proteins. These NETs trap and kill bacteria extracellularly, contributing to a broader antimicrobial response.

**7. Apoptosis and Efferocytosis:** After killing bacteria, neutrophils undergo apoptosis, a programmed cell death process. This ensures that their cytotoxic contents are not released into the surrounding tissue, minimizing damage to healthy cells. Apoptotic neutrophils are then removed by macrophages through efferocytosis, a process that helps to resolve inflammation and prevent secondary infections.

**Conclusion:** Neutrophil-mediated killing of gram-negative bacteria involves a complex series of events, including chemotaxis, phagocytosis, the formation of a phagolysosome, the production of reactive oxygen species, the release of antimicrobial enzymes and peptides, and the formation of NETs. Through these mechanisms, neutrophils effectively eliminate gram-negative bacteria and contribute significantly to the host's defense against infection.'
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Proteins (3)

Compounds (180)