| Summary: | 碩士 === 國立成功大學 === 生理學研究所 === 103 === Innate immune system plays an important role against infections of invading pathogens. Epigenetic mechanisms involving the regulation of chromatin structures, which are divided into “loose” “active” euchromatin and “compact” “silent” heterochromatin states, govern gene expression of physiological systems. However, the molecular and cellular mechanisms by which heterochromatin regulates innate immune responses remain unclear. Here, using Drosophila as the model system, we determined whether and how heterochromatin formation mediates antimicrobial responses to the human pathogen, Pseudomonas aeruginosa PA14, which is Gram-negative and highly virulent. Upon PA14 infection, animals with increased heterochromatin levels survived longer, whereas decreasing heterochromatin exhibits shortened life span. Heterochromatin levels are associated with the activity of the antimicrobial peptide (AMP) gene Drosomycin. Moreover, we found that pirk, an important negative regulator of the Imd pathway, was downregulated in flies with more heterochromatin, and up-regulated in flies with less heterochromatin. Taken together, these data suggest that heterochromatin formation promotes innate antimicrobial responses via downregulating pirk. Our work may contribute to the prevention and treatment of human infectious diseases.
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