論文

査読有り 国際誌
2015年5月5日

Dynamic regulation of innate immune responses in Drosophila by Senju-mediated glycosylation.

Proceedings of the National Academy of Sciences of the United States of America
  • Miki Yamamoto-Hino
  • ,
  • Masatoshi Muraoka
  • ,
  • Shu Kondo
  • ,
  • Ryu Ueda
  • ,
  • Hideyuki Okano
  • ,
  • Satoshi Goto

112
18
開始ページ
5809
終了ページ
14
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1073/pnas.1424514112

The innate immune system is the first line of defense encountered by invading pathogens. Delayed and/or inadequate innate immune responses can result in failure to combat pathogens, whereas excessive and/or inappropriate responses cause runaway inflammation. Therefore, immune responses are tightly regulated from initiation to resolution and are repressed during the steady state. It is well known that glycans presented on pathogens play important roles in pathogen recognition and the interactions between host molecules and microbes; however, the function of glycans of host organisms in innate immune responses is less well known. Here, we show that innate immune quiescence and strength of the immune response are controlled by host glycosylation involving a novel UDP-galactose transporter called Senju. In senju mutants, reduced expression of galactose-containing glycans resulted in hyperactivation of the Toll signaling pathway in the absence of immune challenges. Genetic epistasis and biochemical analyses revealed that Senju regulates the Toll signaling pathway at a step that converts Toll ligand Spatzle to its active form. Interestingly, Toll activation in immune-challenged wild type (WT) flies reduced the expression of galactose-containing glycans. Suppression of the degalactosylation by senju overexpression resulted in reduced induction of Toll-dependent expression of an antimicrobial peptide, Drosomycin, and increased susceptibility to infection with Gram-positive bacteria. These data suggest that Senju-mediated galactosylation suppresses undesirable Toll signaling activation during the steady state; however, Toll activation in response to infection leads to degalactosylation, which raises the immune response to an adequate level and contributes to the prompt elimination of pathogens.

リンク情報
DOI
https://doi.org/10.1073/pnas.1424514112
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/25901322
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4426399
ID情報
  • DOI : 10.1073/pnas.1424514112
  • PubMed ID : 25901322
  • PubMed Central 記事ID : PMC4426399

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