HP1a-mediated heterochromatin formation promotes antimicrobial responses against Pseudomonas aeruginosa infection
Abstract 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 unde...
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| Format: | Article |
| Language: | English |
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BMC
2022-10-01
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| Series: | BMC Biology |
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| Online Access: | https://doi.org/10.1186/s12915-022-01435-8 |
| _version_ | 1811249960022179840 |
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| author | Po-Jen Wu Shian-Jang Yan |
| author_facet | Po-Jen Wu Shian-Jang Yan |
| author_sort | Po-Jen Wu |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-12T15:56:39Z |
| format | Article |
| id | doaj.art-e94c389e6b7847349a737fd1426327e2 |
| institution | Directory Open Access Journal |
| issn | 1741-7007 |
| language | English |
| last_indexed | 2024-04-12T15:56:39Z |
| publishDate | 2022-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Biology |
| spelling | doaj.art-e94c389e6b7847349a737fd1426327e22022-12-22T03:26:21ZengBMCBMC Biology1741-70072022-10-0120111610.1186/s12915-022-01435-8HP1a-mediated heterochromatin formation promotes antimicrobial responses against Pseudomonas aeruginosa infectionPo-Jen Wu0Shian-Jang Yan1Institute of Basic Medical Sciences, College of Medicine, National Cheng-Kung UniversityInstitute of Basic Medical Sciences, College of Medicine, National Cheng-Kung UniversityAbstract 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.https://doi.org/10.1186/s12915-022-01435-8Heterochromatin protein 1a (HP1a)Heterochromatin formationPseudomonas aeruginosaFat bodyAntimicrobial responses |
| spellingShingle | Po-Jen Wu Shian-Jang Yan HP1a-mediated heterochromatin formation promotes antimicrobial responses against Pseudomonas aeruginosa infection BMC Biology Heterochromatin protein 1a (HP1a) Heterochromatin formation Pseudomonas aeruginosa Fat body Antimicrobial responses |
| title | HP1a-mediated heterochromatin formation promotes antimicrobial responses against Pseudomonas aeruginosa infection |
| title_full | HP1a-mediated heterochromatin formation promotes antimicrobial responses against Pseudomonas aeruginosa infection |
| title_fullStr | HP1a-mediated heterochromatin formation promotes antimicrobial responses against Pseudomonas aeruginosa infection |
| title_full_unstemmed | HP1a-mediated heterochromatin formation promotes antimicrobial responses against Pseudomonas aeruginosa infection |
| title_short | HP1a-mediated heterochromatin formation promotes antimicrobial responses against Pseudomonas aeruginosa infection |
| title_sort | hp1a mediated heterochromatin formation promotes antimicrobial responses against pseudomonas aeruginosa infection |
| topic | Heterochromatin protein 1a (HP1a) Heterochromatin formation Pseudomonas aeruginosa Fat body Antimicrobial responses |
| url | https://doi.org/10.1186/s12915-022-01435-8 |
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