A parental transcriptional response to microsporidia infection induces inherited immunity in offspring

Abstract

Parental infection can result in the production of offspring with enhanced immunity phenotypes. Critically, the mechanisms underlying inherited immunity are poorly understood. Here, we show that Caenorhabditis elegans infected with the intracellular microsporidian parasite N. parisii produce progeny that are resistant to microsporidia infection. We determine the kinetics of the response and show that intergenerational immunity prevents host-cell invasion by Nematocida parisii and enhances survival to the bacterial pathogen Pseudomonas aeruginosa. We demonstrate that immunity is induced by the parental transcriptional response to infection, which can be mimicked through maternal somatic depletion of PALS-22 and the retinoblastoma protein ortholog, LIN-35. We find that other biotic and abiotic stresses (viral infection and cadmium exposure) that induce a similar transcriptional response as microsporidia also induce immunity in progeny. Together, our results reveal how a parental transcriptional signal can be induced by distinct stimuli and protect offspring against multiple classes of pathogens.

Intergenerational adaptations to stress are evolutionarily conserved, stress-specific, and have deleterious trade-offs

“…1G). Collectively, our findings indicate that all four reported intergenerational adaptive effects in C. elegans are conserved in at least one other species but all four show a different pattern of conservation, which is consistent with each response being regulated by distinct molecular mechanisms (Burton et al, 2020(Burton et al, , 2017Hibshman et al, 2016;Jordan et al, 2019;Willis et al, 2021).…”

“…To test if any of the intergenerational adaptations to stress that have been reported in C. elegans are evolutionarily conserved in other species we focused on four recently described intergenerational adaptations to abiotic and biotic stresses – osmotic stress ( Burton et al, 2017 ), nutrient stress ( Hibshman et al, 2016 ; Jordan et al, 2019 ), Pseudomonas vranonvensis infection (bacterial) ( Burton et al, 2020 ), and Nematocida parisii infection (eukaryotic – microsporidia) ( Willis et al, 2021 ). All of these stresses are exclusively intergenerational and did not persist beyond two generations in any experimental setup previously analyzed ( Burton et al, 2017 ; Burton et al, 2020 ; Willis et al, 2021 ).…”

“…Percent of animals developing or surviving was scored after 24 hours at room temperature as previously described in Burton et al, 2017 andBurton et al, 2020. Preparation of N. parisii spores. Spores were prepared as described previously (Willis et al, 2021). In brief, large populations of C. elegans N2 were infected with microsporidia spores.…”

“…Multigenerational effects of a parent's environment on progeny have been reported to contribute to numerous organismal phenotypes and pathologies in species ranging from plants to mammals (Agrawal et al, 1999;Bozler et al, 2019;Burton et al, 2020Burton et al, , 2017Dantzer et al, 2013;Dias and Ressler, 2014;Hibshman et al, 2016;Houri-Zeevi et al, 2020;Jordan et al, 2019;Kaletsky et al, 2020;Kishimoto et al, 2017;Klosin et al, 2017;Luna et al, 2012;Ma et al, 2019;Moore et al, 2019;Öst et al, 2014;Palominos et al, 2017;Posner et al, 2019;Veenendaal et al, 2013;Vellichirammal et al, 2017;Webster et al, 2018;Wibowo et al, 2016;Willis et al, 2021).…”

“…Multigenerational effects of a parent’s environment on progeny have been reported to contribute to numerous organismal phenotypes and pathologies in species ranging from plants to mammals ( Agrawal et al, 1999 ; Bozler et al, 2019 ; Burton et al, 2020 ; Burton et al, 2017 ; Dantzer et al, 2013 ; Dias and Ressler, 2014 ; Hibshman et al, 2016 ; Houri-Zeevi et al, 2020 ; Jordan et al, 2019 ; Kaletsky et al, 2020 ; Kishimoto et al, 2017 ; Klosin et al, 2017 ; Luna et al, 2012 ; Ma et al, 2019 ; Moore et al, 2019 ; Öst et al, 2014 ; Palominos et al, 2017 ; Posner et al, 2019 ; Veenendaal et al, 2013 ; Vellichirammal et al, 2017 ; Webster et al, 2018 ; Wibowo et al, 2016 ; Willis et al, 2021 ). These effects on progeny include many notable observations of intergenerational (lasting 1–2 generations) adaptive changes in phenotypically plastic traits such as the development of wings in pea aphids ( Vellichirammal et al, 2017 ), helmet formation in Daphnia ( Agrawal et al, 1999 ), accelerated growth rate in red squirrels ( Dantzer et al, 2013 ), and physiological adaptations to osmotic stress and pathogen infection in both Arabidopsis ( Luna et al, 2012 ; Wibowo et al, 2016 ) and Caenorhabditis elegans ( Burton et al, 2020 ; Burton et al, 2017 ).…”