What is it about?

Mounting an effective immune response is critical when fighting pathogen infection. This study investigated a genetic ‘on/off switch’ in the roundworm C. elegans that regulates immunity against natural pathogens that infect the worm skin and intestine. We identified a mutation in the gene for the ‘on switch’ that results in a protein product that is physically released from repression by the ‘off switch’ protein causing constitutive activation of innate immune programs. Activation of these immune programs was most prominent in the skin of the worm, but we also observed resistance to intracellular pathogens that infect the intestine. Therefore, we hypothesized that immune activation in the skin can signal to the intestine to promote pathogen resistance across these two distinct tissues. Consistent with this hypothesis, we found that skin-specific expression of the ‘on switch’ induced immunity and promoted pathogen resistance in both the skin and the intestine, thus highlighting a novel example of skin-to-intestine immune coordination in a model biological system.

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Why is it important?

When a multicellular organism is infected, immune responses are not always solely restricted to the cells or tissues in contact with the pathogen. The mechanisms of how infection events get sensed, communicated, and responded to across multiple tissues, a process called systemic immunity, is an emergent research area. Our work identified a novel example of genetic regulation of systemic innate immune responses that are coordinated across the skin and intestine in C. elegans. This project sets up future opportunities to uncover molecular mechanisms of cross-tissue regulation of immunity that may be broadly informative across many biological systems.

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This page is a summary of: A pals-25 gain-of-function allele triggers systemic resistance against natural pathogens of C. elegans, PLoS Genetics, October 2022, PLOS,
DOI: 10.1371/journal.pgen.1010314.
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