Caenorhabditis elegans as a model for innate immunity to pathogens

Gravato-Nobre, Maria J.; Hodgkin, Jonathan

doi:10.1111/j.1462-5822.2005.00523.x

Cited by 163 publications

(132 citation statements)

References 86 publications

(130 reference statements)

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“…23 Likewise, virtually all Gram-positive and Gram-negative pathogens studied to date can colonize the brush border microvilli of C. elegans after they successfully escape the grinder and resist antimicrobial peptides in the pharynx, ultimately leading to colonization and distension of the intestinal lumen. 13,21,22 In general, this active infectious process takes place only when the pathogens are cultured on a minimal or "slow-killing" medium, and the extent of colonization often correlates with host killing. Nevertheless, subtle differences have been noticed in terms of the intestinal lumen colonization by these pathogens.…”

Section: Introductionmentioning

confidence: 99%

“…[10][11][12] Over the last decade, there has been a growing appreciation that Caenorhabditis elegans can serve as a simple surrogate host for modeling bacterial diseases. 13 C. elegans is also deemed a relevant host model for studying acute melioidosis. Diabetic patients prone to acute melioidosis have impaired innate immune responses such as macrophage phagocytosis and migration.…”

Section: Introductionmentioning

confidence: 99%

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Burkholderia pseudomalleikillsCaenorhabditis elegansthrough virulence mechanisms distinct from intestinal lumen colonization

et al. 2012

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The nematode Caenorhabditis elegans is hypersusceptible to Burkholderia pseudomallei infection. However, the virulence mechanisms underlying rapid lethality of C. elegans upon B. pseudomallei infection remain poorly defined. To probe the host-pathogen interaction, we constructed GFP-tagged B. pseudomallei and followed bacterial accumulation within the C. elegans intestinal lumen. Contrary to slow-killing by most bacterial pathogens, B. pseudomallei caused fairly limited intestinal lumen colonization throughout the period of observation. Using grinder-defective mutant worms that allow the entry of intact bacteria also did not result in full intestinal lumen colonization. In addition, we observed a significant decline in C. elegans defecation and pharyngeal pumping rates upon B. pseudomallei infection. The decline in defecation rates ruled out the contribution of defecation to the limited B. pseudomallei colonization. We also demonstrated that the limited intestinal lumen colonization was not attributed to slowed host feeding as bacterial loads did not change significantly when feeding was stimulated by exogenous serotonin. Both these observations confirm that B. pseudomallei is a poor colonizer of the C. elegans intestine. To explore the possibility of toxin-mediated killing, we examined the transcription of the C. elegans ABC transporter gene, pgp-5, upon B. pseudomallei infection of the ppgp-5::gfp reporter strain. Expression of pgp-5 was highly induced, notably in the pharynx and intestine, compared with Escherichia coli-fed worms, suggesting that the host actively thwarted the pathogenic assaults during infection. Collectively, our findings propose that B. pseudomallei specifically and continuously secretes toxins to overcome C. elegans immune responses.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Burkholderia pseudomalleikillsCaenorhabditis elegansthrough virulence mechanisms distinct from intestinal lumen colonization

et al. 2012

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“…Specifically, evolutionarily distant organisms, such as plants, mammals, and nematodes, employ a p38 MAP kinase cascade or a TGFb pathway in defense against bacterial and fungal pathogens (for reviews see Millet and Ewbank 2004;Schulenburg et al 2004;Gravato-Nobre and Hodgkin 2005;Sifri et al 2005).…”

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confidence: 99%

Mos1Mutagenesis Reveals a Diversity of Mechanisms Affecting Response ofCaenorhabditis elegansto the Bacterial PathogenMicrobacterium nematophilum

Yook

Hodgkin

2007

Genetics

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A specific host-pathogen interaction exists between Caenorhabditis elegans and the gram-positive bacterium Microbacterium nematophilum. This bacterium is able to colonize the rectum of susceptible worms and induces a defensive tail-swelling response in the host. Previous mutant screens have identified multiple loci that affect this interaction. Some of these loci correspond to known genes, but many bus genes [those with a bacterially unswollen (Bus) mutant phenotype] have yet to be cloned. We employed Mos1 transposon mutagenesis as a means of more rapidly cloning bus genes and identifying new mutants with altered pathogen response. This approach revealed new infection-related roles for two well-characterized and much-studied genes, egl-8 and tax-4. It also allowed the cloning of a known bus gene, bus-17, which encodes a predicted galactosyltransferase, and of a new bus gene, bus-19, which encodes a novel, albeit ancient, protein. The results illustrate advantages and disadvantages of Mos1 transposon mutagenesis in this system.

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“…However, the precise mechanism by which increased temperature mediates innate immunity is not clear. The nematode Caenorhabditis elegans, which has evolved an immune system to recognize pathogens and respond accordingly (2)(3)(4), provides an excellent compromise between complexity and genetic tractability to dissect innate immunity pathways activated by heat stress.…”

mentioning

confidence: 99%

Heat-shock transcription factor (HSF)-1 pathway required for Caenorhabditis elegans immunity

Singh

Aballay

2006

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

209

175

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Innate immunity comprises physical barriers, pattern-recognition receptors, antimicrobial substances, phagocytosis, and fever. Here we report that increased temperature results in the activation of a conserved pathway involving the heat-shock (HS) transcription factor (HSF)-1 that enhances immunity in the invertebrate Caenorhabditis elegans. The HSF-1 defense response is independent of the p38 MAPK͞PMK-1 pathway and requires a system of chaperones including small and 90-kDa inducible HS proteins. In addition, HSF-1 is needed for the effects of the DAF-2 insulin-like pathway in defense to pathogens, indicating that interacting pathways control stress response, aging, and immunity. The results also show that HSF-1 is required for C. elegans immunity against Pseudomonas aeruginosa, Salmonella enterica, Yersinia pestis, and Enterococcus faecalis, indicating that HSF-1 is part of a multipathogen defense pathway. Considering that several coinducers of HSF-1 are currently in clinical trials, this work opens the possibility that activation of HSF-1 could be used to boost immunity to treat infectious diseases and immunodeficiencies.heat-shock protein ͉ innate immunity ͉ MAPK ͉ infection ͉ pathogen I ncreased temperature promotes expression of heat-shock (HS) proteins (HSPs) that are found in high levels in almost all inflammatory diseases (1). However, the precise mechanism by which increased temperature mediates innate immunity is not clear. The nematode Caenorhabditis elegans, which has evolved an immune system to recognize pathogens and respond accordingly (2-4), provides an excellent compromise between complexity and genetic tractability to dissect innate immunity pathways activated by heat stress.A hallmark of C. elegans immunity is activation of defense responses through a conserved p38 MAPK pathway. As in mammalian innate immunity, the p38 MAPK signaling pathway is required for proper C. elegans defense against the human opportunistic pathogen Pseudomonas aeruginosa, which is the major cause of death in cystic fibrosis patients and immunocompromised individuals (5, 6). The pathway also is required to elicit an apoptotic response to Salmonella enterica in the C. elegans germline (7) and for defense to Bacillus thuringiensis toxin Cry5B (8). Based on the fact that C. elegans does not have NF-B-like transcription factors and that the p38 MAPK pathway seems to be more ancient than NF-B (9, 10), it has been postulated that the p38 MAPK pathway is the ancestral immune pathway of a common ancestor of insects, nematodes, and vertebrates (11,12).Although MAPKs have been involved in mammalian defense response and activation of HSPs (13-15), it was unknown whether HSPs and HS transcription factor (HSF)-1 function downstream of the MAPK-mediated immune responses. Here we report that activation of a conserved pathway involving HSF-1 triggers C. elegans immunity to bacterial pathogens. We demonstrate that both small and 90-kDa HSPs activated in an HSF-1-dependent manner are effectors responsible for the immune response. Our res...

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Caenorhabditis elegans as a model for innate immunity to pathogens

Cited by 163 publications

References 86 publications

Burkholderia pseudomalleikillsCaenorhabditis elegansthrough virulence mechanisms distinct from intestinal lumen colonization

Burkholderia pseudomalleikillsCaenorhabditis elegansthrough virulence mechanisms distinct from intestinal lumen colonization

Mos1Mutagenesis Reveals a Diversity of Mechanisms Affecting Response ofCaenorhabditis elegansto the Bacterial PathogenMicrobacterium nematophilum

Heat-shock transcription factor (HSF)-1 pathway required for Caenorhabditis elegans immunity

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