Proteasome inhibition triggers tissue-specific immune responses against different pathogens in C. elegans.
Protein quality control pathways play important roles in resistance against pathogen infection. For example, the conserved transcription factor SKN-1/NRF up-regulates proteostasis capacity after blockade of the proteasome and also promotes resistance against bacterial infection in the nematode Caeno...
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Public Library of Science (PLoS)
2024-03-01
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| Series: | PLoS Biology |
| Online Access: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002543&type=printable |
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| author | Manish Grover Spencer S Gang Emily R Troemel Michalis Barkoulas |
| author_facet | Manish Grover Spencer S Gang Emily R Troemel Michalis Barkoulas |
| author_sort | Manish Grover |
| collection | DOAJ |
| description | Protein quality control pathways play important roles in resistance against pathogen infection. For example, the conserved transcription factor SKN-1/NRF up-regulates proteostasis capacity after blockade of the proteasome and also promotes resistance against bacterial infection in the nematode Caenorhabditis elegans. SKN-1/NRF has 3 isoforms, and the SKN-1A/NRF1 isoform, in particular, regulates proteasomal gene expression upon proteasome dysfunction as part of a conserved bounce-back response. We report here that, in contrast to the previously reported role of SKN-1 in promoting resistance against bacterial infection, loss-of-function mutants in skn-1a and its activating enzymes ddi-1 and png-1 show constitutive expression of immune response programs against natural eukaryotic pathogens of C. elegans. These programs are the oomycete recognition response (ORR), which promotes resistance against oomycetes that infect through the epidermis, and the intracellular pathogen response (IPR), which promotes resistance against intestine-infecting microsporidia. Consequently, skn-1a mutants show increased resistance to both oomycete and microsporidia infections. We also report that almost all ORR/IPR genes induced in common between these programs are regulated by the proteasome and interestingly, specific ORR/IPR genes can be induced in distinct tissues depending on the exact trigger. Furthermore, we show that increasing proteasome function significantly reduces oomycete-mediated induction of multiple ORR markers. Altogether, our findings demonstrate that proteasome regulation keeps innate immune responses in check in a tissue-specific manner against natural eukaryotic pathogens of the C. elegans epidermis and intestine. |
| format | Article |
| id | doaj-art-fec3952dc6294cdba47bf1f925fd0cd5 |
| institution | Kabale University |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2024-03-01 |
| publisher | Public Library of Science (PLoS) |
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| spelling | doaj-art-fec3952dc6294cdba47bf1f925fd0cd52024-11-09T05:30:59ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852024-03-01223e300254310.1371/journal.pbio.3002543Proteasome inhibition triggers tissue-specific immune responses against different pathogens in C. elegans.Manish GroverSpencer S GangEmily R TroemelMichalis BarkoulasProtein quality control pathways play important roles in resistance against pathogen infection. For example, the conserved transcription factor SKN-1/NRF up-regulates proteostasis capacity after blockade of the proteasome and also promotes resistance against bacterial infection in the nematode Caenorhabditis elegans. SKN-1/NRF has 3 isoforms, and the SKN-1A/NRF1 isoform, in particular, regulates proteasomal gene expression upon proteasome dysfunction as part of a conserved bounce-back response. We report here that, in contrast to the previously reported role of SKN-1 in promoting resistance against bacterial infection, loss-of-function mutants in skn-1a and its activating enzymes ddi-1 and png-1 show constitutive expression of immune response programs against natural eukaryotic pathogens of C. elegans. These programs are the oomycete recognition response (ORR), which promotes resistance against oomycetes that infect through the epidermis, and the intracellular pathogen response (IPR), which promotes resistance against intestine-infecting microsporidia. Consequently, skn-1a mutants show increased resistance to both oomycete and microsporidia infections. We also report that almost all ORR/IPR genes induced in common between these programs are regulated by the proteasome and interestingly, specific ORR/IPR genes can be induced in distinct tissues depending on the exact trigger. Furthermore, we show that increasing proteasome function significantly reduces oomycete-mediated induction of multiple ORR markers. Altogether, our findings demonstrate that proteasome regulation keeps innate immune responses in check in a tissue-specific manner against natural eukaryotic pathogens of the C. elegans epidermis and intestine.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002543&type=printable |
| spellingShingle | Manish Grover Spencer S Gang Emily R Troemel Michalis Barkoulas Proteasome inhibition triggers tissue-specific immune responses against different pathogens in C. elegans. PLoS Biology |
| title | Proteasome inhibition triggers tissue-specific immune responses against different pathogens in C. elegans. |
| title_full | Proteasome inhibition triggers tissue-specific immune responses against different pathogens in C. elegans. |
| title_fullStr | Proteasome inhibition triggers tissue-specific immune responses against different pathogens in C. elegans. |
| title_full_unstemmed | Proteasome inhibition triggers tissue-specific immune responses against different pathogens in C. elegans. |
| title_short | Proteasome inhibition triggers tissue-specific immune responses against different pathogens in C. elegans. |
| title_sort | proteasome inhibition triggers tissue specific immune responses against different pathogens in c elegans |
| url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.3002543&type=printable |
| work_keys_str_mv | AT manishgrover proteasomeinhibitiontriggerstissuespecificimmuneresponsesagainstdifferentpathogensincelegans AT spencersgang proteasomeinhibitiontriggerstissuespecificimmuneresponsesagainstdifferentpathogensincelegans AT emilyrtroemel proteasomeinhibitiontriggerstissuespecificimmuneresponsesagainstdifferentpathogensincelegans AT michalisbarkoulas proteasomeinhibitiontriggerstissuespecificimmuneresponsesagainstdifferentpathogensincelegans |