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.

Microsporidia are a large group of parasites that cause death and disease in humans and many agriculturally important animal species. To fully understand the diverse properties of these parasites, we curated species reports from the last 160 years.

Inherited immunity is an emerging field and describes how the transfer of immunity from parents to offspring can promote progeny survival in the face of infection. The mechanisms of how inherited immunity is induced are mostly unknown. The intracellular parasite Nematocida parisii is a natural microsporidian pathogen of Caenorhabditis elegans. Here, we show that N. parisii-infected worms produce primed offspring that are resistant to microsporidia infection. We find that immunity is induced in a dose dependent manner and lasts for a single generation. Intergenerational immunity prevents host cell invasion by N. parisii and also enhances survival to the bacterial pathogen Pseudomonas aeruginosa. Further, we show that inherited immunity is triggered by the host transcriptional response to infection, which can also be induced through maternal somatic depletion of negative regulators PALS-22 and the retinoblastoma protein ortholog LIN-35. We show that other biotic and abiotic stresses, such as viral infection and cadmium exposure, that induce a similar transcriptional response to microsporidia can also induce immunity in progeny. Our results demonstrate that distinct stimuli can induce inherited immunity to provide resistance against multiple classes of pathogens. These results show that activation of an innate immune response can provide protection against pathogens not only within a generation, but also in the next generation.

Microsporidia are a large group of fungal-related obligate intracellular parasites. Though many microsporidia species have been identified over the past 160 years, there is a lacking depiction of the full diversity of this phylum. To systematically describe the characteristics of these parasites, we created a database of 1,428 species and their attributes, including the hosts they infect and spore characteristics. We find that microsporidia have been reported to infect 15 metazoan and four protozoan phyla, with smaller phyla being underrepresented. Most species are only reported to infect a single host, but those that are generalists are also more likely to infect a broader set of host tissues. Strikingly, polar tubes are 3-fold longer in species that infect tissues besides the intestine, suggesting that polar tube length is a determinant of tissue specificity. Phylogenetic analysis revealed four clades which each contain microsporidia infecting hosts from all major habitats. Although related species are more likely to infect similar hosts, we observe examples of changes in host specificity and convergent evolution. Taken together, our results show that microsporidia display vast diversity in their morphology and the hosts they infect, illustrating the flexibility of these parasites to evolve new traits.

Exposure of animals to diverse stimuli causes priming of their innate immune defences which can protect them from subsequent infections. Using C. elegans, mechanisms of immune memory against bacterial and viral pathogens have been determined. Prior exposure causes sustained upregulation of innate immune gene expression. Animals can also learn to avoid pathogenic bacteria. Remarkably, immunity can be transmitted to progeny to enhance pathogen resistance in future generations.