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Abstract
How phagocytes find invading microorganisms and eliminate pathogenic ones from human bodies is a fundamental question in the study of infectious diseases. About 2.5 billion years ago, eukaryotic unicellular organisms–protozoans–appeared and started to interact with various bacteria. Less than 1 billion years ago, multicellular animals–metazoans–appeared and acquired the ability to distinguish self from non-self and to remove harmful organisms from their bodies. Since then, animals have developed innate immunity in which specialized white-blood cells phagocytes- patrol the body to kill pathogenic bacteria. The social amoebae Dictyostelium discoideum are prototypical phagocytes that chase various bacteria via chemotaxis and consume them as food via phagocytosis. Studies of this genetically amendable organism have revealed evolutionarily conserved mechanisms underlying chemotaxis and phagocytosis and shed light on studies of phagocytes in mammals. In this review, we briefly summarize important studies that contribute to our current understanding of how phagocytes effectively find and kill pathogens via chemotaxis and phagocytosis.
Highlights
How eukaryotic cells interact with bacteria and viruses is a fundamental question in biology
In 1882, Metchnikoff first noted that cells migrated from afar and covered a rose thorn inserted into the larva of a starfish (Beck and Habicht, 1996), and Leber (1888) discovered that leukocytes migrated in straight paths to sites of rabbit corneal irritation (Mc, 1946)
Recent studies revealed that S cells use Toll/interleukin1 receptor (TIR) domain protein, TirA, to recognize bacteria, produce extracellular traps (ETs) and reactive oxygen species to kill bacteria in the slug of D. discoideum (Chen et al, 2007; Zhang et al, 2016)
Summary
How eukaryotic cells interact with bacteria and viruses is a fundamental question in biology. In 1882, Metchnikoff first noted that cells migrated from afar and covered a rose thorn inserted into the larva of a starfish (Beck and Habicht, 1996), and Leber (1888) discovered that leukocytes migrated in straight paths to sites of rabbit corneal irritation (Mc, 1946) Those observations gave rise to the hypothesis that diffusible substances generated by a foreign object or at the site of injury establish chemical gradients that guide cell migration. It became a paradigm that phagocytes use GPCRs to detect diffusible chemicals (both classical chemoattractants and chemokines) and to mediate signaling pathways that control the reorganization of the actin cytoskeleton for cell migration toward the sites of infection and pathogens via chemotaxis. The model system D. discoideum has been used to raise fundamental questions in eukaryotic chemotaxis, propose hypotheses of gradient sensing, discover essential components involved in chemotaxis, and develop techniques to study chemotaxis
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