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Functional genomic analysis of phagocytosis and identification of a Drosophila receptor for E. coli.

Publication ,  Journal Article
Rämet, M; Manfruelli, P; Pearson, A; Mathey-Prevot, B; Ezekowitz, RAB
Published in: Nature
April 11, 2002

The recognition and phagocytosis of microbes by macrophages is a principal aspect of innate immunity that is conserved from insects to humans. Drosophila melanogaster has circulating macrophages that phagocytose microbes similarly to mammalian macrophages, suggesting that insect macrophages can be used as a model to study cell-mediated innate immunity. We devised a double-stranded RNA interference-based screen in macrophage-like Drosophila S2 cells, and have defined 34 gene products involved in phagocytosis. These include proteins that participate in haemocyte development, vesicle transport, actin cytoskeleton regulation and a cell surface receptor. This receptor, Peptidoglycan recognition protein LC (PGRP-LC), is involved in phagocytosis of Gram-negative but not Gram-positive bacteria. Drosophila humoral immunity also distinguishes between Gram-negative and Gram-positive bacteria through the Imd and Toll pathways, respectively; however, a receptor for the Imd pathway has not been identified. Here we show that PGRP-LC is important for antibacterial peptide synthesis induced by Escherichia coli both in vitro and in vivo. Furthermore, totem mutants, which fail to express PGRP-LC, are susceptible to Gram-negative (E. coli), but not Gram-positive, bacterial infection. Our results demonstrate that PGRP-LC is an essential component for recognition and signalling of Gram-negative bacteria. Furthermore, this functional genomic approach is likely to have applications beyond phagocytosis.

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Published In

Nature

DOI

ISSN

0028-0836

Publication Date

April 11, 2002

Volume

416

Issue

6881

Start / End Page

644 / 648

Location

England

Related Subject Headings

  • Survival Rate
  • Staphylococcus aureus
  • Species Specificity
  • Signal Transduction
  • RNA, Messenger
  • RNA, Double-Stranded
  • Phagocytosis
  • Oligonucleotide Array Sequence Analysis
  • Macrophages
  • Hemocytes
 

Citation

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Rämet, M., Manfruelli, P., Pearson, A., Mathey-Prevot, B., & Ezekowitz, R. A. B. (2002). Functional genomic analysis of phagocytosis and identification of a Drosophila receptor for E. coli. Nature, 416(6881), 644–648. https://doi.org/10.1038/nature735
Rämet, Mika, Pascal Manfruelli, Alan Pearson, Bernard Mathey-Prevot, and R Alan B. Ezekowitz. “Functional genomic analysis of phagocytosis and identification of a Drosophila receptor for E. coli.Nature 416, no. 6881 (April 11, 2002): 644–48. https://doi.org/10.1038/nature735.
Rämet M, Manfruelli P, Pearson A, Mathey-Prevot B, Ezekowitz RAB. Functional genomic analysis of phagocytosis and identification of a Drosophila receptor for E. coli. Nature. 2002 Apr 11;416(6881):644–8.
Rämet, Mika, et al. “Functional genomic analysis of phagocytosis and identification of a Drosophila receptor for E. coli.Nature, vol. 416, no. 6881, Apr. 2002, pp. 644–48. Pubmed, doi:10.1038/nature735.
Rämet M, Manfruelli P, Pearson A, Mathey-Prevot B, Ezekowitz RAB. Functional genomic analysis of phagocytosis and identification of a Drosophila receptor for E. coli. Nature. 2002 Apr 11;416(6881):644–648.
Journal cover image

Published In

Nature

DOI

ISSN

0028-0836

Publication Date

April 11, 2002

Volume

416

Issue

6881

Start / End Page

644 / 648

Location

England

Related Subject Headings

  • Survival Rate
  • Staphylococcus aureus
  • Species Specificity
  • Signal Transduction
  • RNA, Messenger
  • RNA, Double-Stranded
  • Phagocytosis
  • Oligonucleotide Array Sequence Analysis
  • Macrophages
  • Hemocytes