Abstract
Understanding the roles of neutrophils and macrophages in fighting bacterial infections is a critical issue in human pathologies. Although phagocytic killing has been extensively studied, little is known about how bacteria are eliminated extracellularly in live vertebrates. We have recently developed an infection model in the zebrafish embryo in which leukocytes cannot reach the injected bacteria. When Escherichia coli bacteria are injected within the notochord, both neutrophils and macrophages are massively recruited during several days, but do not infiltrate the infected tissue presumably because of its tough collagen sheath. Nevertheless, the bacteria are killed during the first 24 hours, and we report here that neutrophils, but not macrophages are involved in the control of the infection. Using genetic and chemical approaches, we show that even in absence of phagocytosis, the bactericidal action relies on NADPH oxidase-dependent production of superoxide in neutrophils. We thus reveal a host effector mechanism mediated by neutrophils that eliminates bacteria that cannot be reached by phagocytes and that is independent of macrophages, NO synthase or myeloperoxidase.
Highlights
The innate immune system is the first line of defence of the host
Phagocytic killing has been extensively studied, little is known about how bacteria are eliminated extracellularly in live vertebrates
We use the notochord infection model in the zebrafish embryo to describe how leukocytes eliminate distant bacteria that are inaccessible for phagocytosis
Summary
The innate immune system is the first line of defence of the host. It includes large phagocytes (such as macrophages and granulocytes) equipped with a battery of weapons to destroy the invader within minutes or hours. When microbes penetrate the epithelial barrier, macrophages and neutrophils are rapidly recruited and upon contact, engulf the bacteria into a vacuole called a phagosome that fuses with intracellular granules or lysosomes to form a lytic vacuole in which bacteria may be killed by a wide variety of mechanisms involving chemicals and enzymes [2,3]. Nitric oxide (NO), produced by NO synthase, can contribute to microbicidal activity and is essential for the defence against intracellular organisms such as Salmonella enterica and mycobacteria [9,10]
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