HP1a-mediated heterochromatin formation promotes antimicrobial responses against Pseudomonas aeruginosa infection

Po Jen Wu, Shian Jang Yan

研究成果: Article同行評審

1 引文 斯高帕斯(Scopus)

摘要

Background: Pseudomonas aeruginosa is a Gram-negative bacterium that causes severe infectious disease in diverse host organisms, including humans. Effective therapeutic options for P. aeruginosa infection are limited due to increasing multidrug resistance and it is therefore critical to understand the regulation of host innate immune responses to guide development of effective therapeutic options. The epigenetic mechanisms by which hosts regulate their antimicrobial responses against P. aeruginosa infection remain unclear. Here, we used Drosophila melanogaster to investigate the role of heterochromatin protein 1a (HP1a), a key epigenetic regulator, and its mediation of heterochromatin formation in antimicrobial responses against PA14, a highly virulent P. aeruginosa strain. Results: Animals with decreased heterochromatin levels showed less resistance to P. aeruginosa infection. In contrast, flies with increased heterochromatin formation, either in the whole organism or specifically in the fat body—an organ important in humoral immune response—showed greater resistance to P. aeruginosa infection, as demonstrated by increased host survival and reduced bacterial load. Increased heterochromatin formation in the fat body promoted the antimicrobial responses via upregulation of fat body immune deficiency (imd) pathway-mediated antimicrobial peptides (AMPs) before and in the middle stage of P. aeruginosa infection. The fat body AMPs were required to elicit HP1a-mediated antimicrobial responses against P. aeruginosa infection. Moreover, the levels of heterochromatin in the fat body were downregulated in the early stage, but upregulated in the middle stage, of P. aeruginosa infection. Conclusions: These data indicate that HP1a-mediated heterochromatin formation in the fat body promotes antimicrobial responses by epigenetically upregulating AMPs of the imd pathway. Our study provides novel molecular, cellular, and organismal insights into new epigenetic strategies targeting heterochromatin that have the potential to combat P. aeruginosa infection.

原文English
文章編號234
期刊BMC Biology
20
發行號1
DOIs
出版狀態Published - 2022 12月

All Science Journal Classification (ASJC) codes

  • 生物技術
  • 結構生物學
  • 生態學、進化論、行為學與系統學
  • 生理學
  • 一般生物化學,遺傳學和分子生物學
  • 一般農業與生物科學
  • 植物科學
  • 發展生物學
  • 細胞生物學

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