PALS-14 promotes resistance to infection in .

Microsporidia are common natural pathogens of the nematode . Infection of by the microsporidian species leads to induction of the Intracellular Pathogen Response (IPR), including transcriptional upregulation of 26 genes. The divergent ' ' sequence signature is conserved with humans, but PALS proteins have unknown biochemical functions.

RIG-I-like receptor DRH-1 signals via CARDs to activate antiviral immunity in intestinal cells.

Upon sensing viral RNA, mammalian RIG-I-like receptors (RLRs) activate downstream signals using caspase activation and recruitment domains (CARDs), which ultimately promote transcriptional immune responses that have been well studied. In contrast, the downstream signaling mechanisms for invertebrate RLRs are much less clear. For example, the RLR DRH-1 lacks annotated CARDs and up-regulates the distinct output of RNA interference.

Orsay Virus Infection in Caenorhabditis elegans.

Orsay virus infection in the nematode Caenorhabditis elegans presents an opportunity to study host-virus interactions in an easily culturable, whole-animal host. Previously, a major limitation of C. elegans as a model for studying antiviral immunity was the lack of viruses known to naturally infect the worm.

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 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.

RIG-I-like receptor DRH-1 signals via CARDs to activate anti-viral immunity in intestinal cells.

Upon sensing viral RNA, mammalian RIG-I-like receptors activate downstream signals using caspase activation and recruitment domains (CARDs), which ultimately promote transcriptional immune responses that have been well-studied. In contrast, the downstream signaling mechanisms for invertebrate RIG-I-like receptors are much less clear. For example, the RIG-I-like receptor DRH-1 lacks annotated CARDs and upregulates the distinct output of RNA interference (RNAi).

Similarities in the induction of the intracellular pathogen response in Caenorhabditis elegans and the type I interferon response in mammals.

Although the type-I interferon (IFN-I) response is considered vertebrate-specific, recent findings about the Intracellular Pathogen Response (IPR) in nematode Caenorhabditis elegans indicate that there are similarities between these two transcriptional immunological programs. The IPR is induced during infection with natural intracellular fungal and viral pathogens of the intestine and promotes resistance against these pathogens. Similarly, the IFN-I response is induced by viruses and other intracellular pathogens and promotes resistance against infection.

Multiple pals gene modules control a balance between immunity and development in Caenorhabditis elegans.

The immune system continually battles against pathogen-induced pressures, which often leads to the evolutionary expansion of immune gene families in a species-specific manner. For example, the pals gene family expanded to 39 members in the Caenorhabditis elegans genome, in comparison to a single mammalian pals ortholog. Our previous studies have revealed that two members of this family, pals-22 and pals-25, act as antagonistic paralogs to control the Intracellular Pathogen Response (IPR).

Multiple gene modules control a balance between immunity and development in .

Unlabelled: The immune system continually battles against pathogen-induced pressures, which often leads to the evolutionary expansion of immune gene families in a species-specific manner. For example, the gene family expanded to 39 members in the genome, in comparison to a single mammalian ortholog. Our previous studies have revealed that two members of this family, and , act as antagonistic paralogs to control the Intracellular Pathogen Response (IPR).

Conservation of Nematocida microsporidia gene expression and host response in Caenorhabditis nematodes.

Microsporidia are obligate intracellular parasites that are known to infect most types of animals. Many species of microsporidia can infect multiple related hosts, but it is not known if microsporidia express different genes depending upon which host species is infected or if the host response to infection is specific to each microsporidia species. To address these questions, we took advantage of two species of Nematocida microsporidia, N.

A pals-25 gain-of-function allele triggers systemic resistance against natural pathogens of C. elegans.

Regulation of immunity throughout an organism is critical for host defense. Previous studies in the nematode Caenorhabditis elegans have described an "ON/OFF" immune switch comprised of the antagonistic paralogs PALS-25 and PALS-22, which regulate resistance against intestinal and epidermal pathogens. Here, we identify and characterize a PALS-25 gain-of-function mutant protein with a premature stop (Q293*), which we find is freed from physical repression by its negative regulator, the PALS-22 protein.

Correction: The purine nucleoside phosphorylase pnp-1 regulates epithelial cell resistance to infection in C. elegans.

[This corrects the article DOI: 10.1371/journal.ppat.

Insights from C. elegans into Microsporidia Biology and Host-Pathogen Relationships.

Microsporidia are poorly understood, ubiquitous eukaryotic parasites that are completely dependent on their hosts for replication. With the discovery of microsporidia species naturally infecting the genetically tractable transparent nematode C. elegans, this host has been used to explore multiple areas of microsporidia biology.

The purine nucleoside phosphorylase pnp-1 regulates epithelial cell resistance to infection in C. elegans.

Intestinal epithelial cells are subject to attack by a diverse array of microbes, including intracellular as well as extracellular pathogens. While defense in epithelial cells can be triggered by pattern recognition receptor-mediated detection of microbe-associated molecular patterns, there is much to be learned about how they sense infection via perturbations of host physiology, which often occur during infection. A recently described host defense response in the nematode C.

Conservation lost: host-pathogen battles drive diversification and expansion of gene families.

One of the strongest drivers in evolution is the struggle to survive a host-pathogen battle. This pressure selects for diversity among the factors directly involved in this battle, including virulence factors deployed by pathogens, their corresponding host targets, and host immune factors. A logical outcome of this diversification is that over time, the sequence of many immune factors will not be evolutionarily conserved across a broad range of species.

A cullin-RING ubiquitin ligase promotes thermotolerance as part of the intracellular pathogen response in .

Intracellular pathogen infection leads to proteotoxic stress in host organisms. Previously we described a physiological program in the nematode called the intracellular pathogen response (IPR), which promotes resistance to proteotoxic stress and appears to be distinct from canonical proteostasis pathways. The IPR is controlled by PALS-22 and PALS-25, proteins of unknown biochemical function, which regulate expression of genes induced by natural intracellular pathogens.

The Caenorhabditis elegans RIG-I Homolog DRH-1 Mediates the Intracellular Pathogen Response upon Viral Infection.

Mammalian retinoic acid-inducible gene I (RIG-I)-like receptors detect viral double-stranded RNA (dsRNA) and 5'-triphosphorylated RNA to activate the transcription of interferon genes and promote antiviral defense. The RIG-I-like receptor DRH-1 promotes defense through antiviral RNA interference (RNAi), but less is known about its role in regulating transcription. Here, we describe a role for DRH-1 in directing a transcriptional response in called the intracellular pathogen response (IPR), which is associated with increased pathogen resistance.

Nanoluciferase-Based Method for Detecting Gene Expression in .

Genetic reporters such as the green fluorescent protein (GFP) can facilitate measurement of promoter activity and gene expression. However, animal autofluorescence limits the sensitivity of GFP and other fluorescent reporters in whole-animal settings like in the nematode Here, we present a highly sensitive Nanoluciferase (NanoLuc)-based method in a multiwell format to detect constitutive and inducible gene expression in We optimize detection of bioluminescent signals from NanoLuc in and show that it can be detected at 400,000-fold over background in a population of 100 animals expressing intestinal NanoLuc driven by the promoter. We can reliably detect signal in single ::-expressing worms from all developmental stages.

Natural variation in the roles of C. elegans autophagy components during microsporidia infection.

Natural genetic variation can determine the outcome of an infection, and often reflects the co-evolutionary battle between hosts and pathogens. We previously found that a natural variant of the nematode Caenorhabditis elegans from Hawaii (HW) has increased resistance against natural microsporidian pathogens in the Nematocida genus, when compared to the standard laboratory strain of N2. In particular, HW animals can clear infection, while N2 animals cannot.

Antagonistic paralogs control a switch between growth and pathogen resistance in C. elegans.

Immune genes are under intense, pathogen-induced pressure, which causes these genes to diversify over evolutionary time and become species-specific. Through a forward genetic screen we recently described a C. elegans-specific gene called pals-22 to be a repressor of "Intracellular Pathogen Response" or IPR genes.

Host-parasite interactions: an interview with Emily Troemel.

Emily Troemel is a Professor at the University of California San Diego, where her lab uses Caenorhabditis elegans to study host-pathogen interactions and the shaping of the immune response. In this interview, Emily shared her thoughts on peer review and its role in training future scientists, and the possibility of a new form of immunity in epithelia.

Autophagy and innate immunity: Insights from invertebrate model organisms.

Macroautophagy/autophagy is a fundamental intracellular degradation process with multiple roles in immunity, including direct elimination of intracellular microorganisms via 'xenophagy.' In this review, we summarize studies from the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans that highlight the roles of autophagy in innate immune responses to viral, bacterial, and fungal pathogens. Research from these genetically tractable invertebrates has uncovered several conserved immunological paradigms, such as direct targeting of intracellular pathogens by xenophagy and regulation of autophagy by pattern recognition receptors in D.