Recognition of Pathogenic Microbes by the Drosophila Phagocytic Pattern Recognition Receptor Eater
| Autor: | Yoon-Suk Alexander Chung, Christine Kocks |
|---|---|
| Rok vydání: | 2011 |
| Předmět: |
Immunology
Antimicrobial peptides Receptors Cell Surface Gram-Positive Bacteria medicine.disease_cause Biochemistry Microbiology Phagocytosis Gram-Negative Bacteria medicine Animals Drosophila Proteins Receptor Molecular Biology Escherichia coli Phagocytes Innate immune system biology Pattern recognition receptor Cell Biology biology.organism_classification Drosophila melanogaster Serratia marcescens Additions and Corrections Bacteria Antimicrobial Cationic Peptides |
| Zdroj: | Journal of Biological Chemistry. 286:26524-26532 |
| ISSN: | 0021-9258 |
| Popis: | Non-opsonic phagocytosis is a primordial form of pathogen recognition that is mediated by the direct interaction of phagocytic receptors with microbial surfaces. In the fruit fly Drosophila melanogaster, the EGF-like repeat containing scavenger receptor Eater is expressed by phagocytes and is required to survive infections with Gram-positive and Gram-negative bacteria. However, the mechanisms by which this receptor recognizes different types of bacteria are poorly understood. To address this problem, we generated a soluble, Fc-tagged receptor variant of Eater comprising the N-terminal 199 amino acids including four EGF-like repeats. We first established that Eater-Fc displayed specific binding to broad yet distinct classes of heat- or ethanol-inactivated microbes and behaved similarly to the membrane-bound, full-length Eater receptor. We then used Eater-Fc as a tool to probe Eater binding to the surface of live bacteria. Eater-Fc bound equally well to naive or inactivated Staphylococcus aureus or Enterococcus faecalis, suggesting that in vivo, Eater directly targets live Gram-positive bacteria, enabling their phagocytic clearance and destruction. By contrast, Eater-Fc was unable to interact with live, naive Gram-negative bacteria (Escherichia coli, Serratia marcescens, and Pseudomonas aeruginosa). For these bacteria, Eater-Fc binding required membrane-disrupting treatments. Furthermore, we found that cecropin A, a cationic, membrane-disrupting antimicrobial peptide, could promote Eater-Fc binding to live E. coli, even at sublethal concentrations. These results suggest a previously unrecognized mechanism by which antimicrobial peptides cooperate with phagocytic receptors to extend the range of microbes that can be targeted by a single, germline-encoded receptor. |
| Databáze: | OpenAIRE |
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