Evolution of host innate defence: insights from Caenorhabditis elegans and primitive invertebrates

Irazoqui, Javier E.; Urbach, Jonathan M.; Ausubel, Frederick M.

doi:10.1038/nri2689

Cited by 361 publications

(377 citation statements)

References 121 publications

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“…This shows that TLR signaling in Hydra does not act unidirectionally via the transcription factor NF-κB but is also linked to MAP kinases. Notably, a p38 MAPK cascade was identified as a key component of the C. elegans immune response and is also present in Monosiga brevicollis, a single-cell eukaryote that is most closely related to metazoans (22). Because JNK and p38 in Hydra are also activated by many other stimuli, including G-protein-coupled receptors (38) and the wnt pathway (34), innate immune reactions appear to be controlled by a complex signal transduction network.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, Toll (5, 6) as well as Toll-7 (7) and Toll-8 (8) act in immune defense against fungi, bacteria, or viruses. This functional duality prompted us to search for the ancestral role of TLR signaling in a more basal metazoan (22). The cnidarian Hydra possesses a bona fide TLR-signaling cascade (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…However, recent genome projects in the nonbilaterians Hydra magnipapillata (18) and Nematostella vectensis (19) revealed the presence of TLRs, MyD88, and NF-κB (20,21). Their role in bacterial recognition and innate immunity, however, remains to be shown (22). Cnidaria are a sister group to the Bilateria (19) and one of the earliest branches in the animal tree of life (Fig.…”

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confidence: 99%

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MyD88-deficient Hydra reveal an ancient function of TLR signaling in sensing bacterial colonizers

Franzenburg

Fraune

Künzel

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

145

144

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Toll-like receptor (TLR) signaling is one of the most important signaling cascades of the innate immune system of vertebrates. Studies in invertebrates have focused on the fruit fly Drosophila melanogaster and the nematode Caenorhabditis elegans, and there is little information regarding the evolutionary origin and ancestral function of TLR signaling. In Drosophila, members of the Toll-like receptor family are involved in both embryonic development and innate immunity. In C. elegans, a clear immune function of the TLR homolog TOL-1 is controversial and central components of vertebrate TLR signaling including the key adapter protein myeloid differentiation primary response gene 88 (MyD88) and the transcription factor NF-κB are not present. In basal metazoans such as the cnidarians Hydra magnipapillata and Nematostella vectensis, all components of the vertebrate TLR signaling cascade are present, but their role in immunity is unknown. Here, we use a MyD88 lossof-function approach in Hydra to demonstrate that recognition of bacteria is an ancestral function of TLR signaling and that this process contributes to both host-mediated recolonization by commensal bacteria as well as to defense against bacterial pathogens.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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MyD88-deficient Hydra reveal an ancient function of TLR signaling in sensing bacterial colonizers

Franzenburg

Fraune

Künzel

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

145

144

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“…The nematode Caenorhabditis elegans has recently emerged as a small-animal model for innate immunity studies (10,11). Genetic studies indicate that antiviral RNAi in C. elegans requires the genes essential for RNAi induced by exogenous dsRNA (12)(13)(14)(15)(16)(17).…”

mentioning

confidence: 99%

Homologous RIG-I–like helicase proteins direct RNAi-mediated antiviral immunity in C. elegans by distinct mechanisms

Guo

Zhang

Wang

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

128

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RNAi-mediated antiviral immunity in Caenorhabditis elegans requires Dicer-related helicase 1 (DRH-1), which encodes the helicase and C-terminal domains homologous to the mammalian retinoic acid inducible gene I (RIG-I)-like helicase (RLH) family of cytosolic immune receptors. Here we show that the antiviral function of DRH-1 requires the RIG-I homologous domains as well as its wormspecific N-terminal domain. We also demonstrate that the helicase and C-terminal domains encoded by either worm DRH-2 or human RIG-I can functionally replace the corresponding domains of DRH-1 to mediate antiviral RNAi in C. elegans. Notably, substitutions in a three-residue motif of the C-terminal regulatory domain of RIG-I that physically interacts with viral double-stranded RNA abolish the antiviral activity of C-terminal regulatory domains of both RIG-I and DRH-1 in C. elegans. Genetic analysis revealed an essential role for both DRH-1 and DRH-3 in C. elegans antiviral RNAi targeting a natural viral pathogen. However, Northern blot and small RNA deep sequencing analyses indicate that DRH-1 acts to enhance production of viral primary siRNAs, whereas DRH-3 regulates antiviral RNAi by participating in the biogenesis of secondary siRNAs after Dicer-dependent production of primary siRNAs. We propose that DRH-1 facilitates the acquisition of viral double-stranded RNA by the worm dicing complex for the subsequent processing into primary siRNAs. The strong parallel for the antiviral function of RLHs in worms and mammals suggests that detection of viral doublestranded RNA may activate completely unrelated effector mechanisms or, alternatively, that the mammalian RLHs have a conserved activity to stimulate production of viral siRNAs for antiviral immunity by an RNAi effector mechanism.I nnate immunity refers to ancient host defense systems that act immediately after pathogen attack and are under the control of germline-encoded immune receptors. Pathogen sensing by several classes of immune receptors such as retinoic acid inducible gene I (RIG-I)-like cytosolic sensors in mammals leads to the transcriptional activation of effector genes in the nucleus (1). In contrast, detection of viral double-stranded RNA (dsRNA) by Dicer endonucleases is associated with the production of small interfering RNAs (siRNAs), which subsequently direct sequencespecific antiviral immunity through RNA interference (RNAi) (2-5). Antiviral RNAi is a major antiviral defense mechanism in fungi, plants, insects, and nematodes, so that suppression of the defense by a virus-encoded suppressor of RNAi is essential to establish infection (6-8). Although the RNAi machinery is highly conserved in mammals, conclusive evidence for a natural antiviral role of RNAi in mammals is not available (9).The nematode Caenorhabditis elegans has recently emerged as a small-animal model for innate immunity studies (10, 11). Genetic studies indicate that antiviral RNAi in C. elegans requires the genes essential for RNAi induced by exogenous dsRNA (12-17). These include Dicer-1 and dsRNA-bind...

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“…elicited negligible changes in the physiological characteristics of C. elegans , including size, compared with those of worms given E. coli OP50 as a control (data not shown) for 24 h. Remarkably, the viability of C. elegans was significantly enhanced. When they were pre-exposed to the non-pathogenic E. coli OP50 strain [46]. The chemotaxis assay has been used to reveal the behavioural characteristics of nematodes in the field of neurobiology [47].…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo defensive effect of probiotic LAB against Pseudomonas aeruginosa using Caenorhabditis elegans model

et al. 2018

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This study aimed to investigate in vitro and in vivo the probiotic characteristics of lactic acid bacteria (LAB) isolated from Korean traditional fermented foods. Caenorhabditis elegans (C. elegans) was used for analytical assays of fertility, chemotaxis, life-span, worm-killing and bacterial colonization in the intestinal lumen of the worm. All 35 strains of LAB reduced fertility and slowed development in the worms. The worm-killing assay showed that LAB significantly increased the lifespan (P < 0.05) and reduced the susceptibility to virulent PA14; however, the heat-killed LAB did not. The bacterial colonization assay revealed that LAB proliferated and protected the gut of the worm against infection by Pseudomonas aeruginosa PA14. In addition, specific LAB Pediococcus acidilactici(P. acidilactici DM-9), Pediococcus brevis (L. brevis SDL1411), and Pediococcus pentosaceus (P. pentosaceus SDL1409) strains showed acid resistance (66–91%), resistance to pepsin (64–67%) and viability in simulated intestinal fluid (67–73%) based on in vitro probiotic analyses. Taken together, these results suggest that C. elegans may be a tractable model for screening efficient probiotics.

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Evolution of host innate defence: insights from Caenorhabditis elegans and primitive invertebrates

Cited by 361 publications

References 121 publications

MyD88-deficient Hydra reveal an ancient function of TLR signaling in sensing bacterial colonizers

MyD88-deficient Hydra reveal an ancient function of TLR signaling in sensing bacterial colonizers

Homologous RIG-I–like helicase proteins direct RNAi-mediated antiviral immunity in C. elegans by distinct mechanisms

In vitro and in vivo defensive effect of probiotic LAB against Pseudomonas aeruginosa using Caenorhabditis elegans model

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