Recovery from an Acute Infection in C. Elegans Requires the GATA Transcription Factor ELT-2

Overview

Journal PLoS Genet

Specialty Genetics

Date 2014 Oct 24

PMID 25340560

Citations 11

Authors

Brian Head

Alejandro Aballay

Affiliations

Soon will be listed here.

Abstract

The mechanisms involved in the recognition of microbial pathogens and activation of the immune system have been extensively studied. However, the mechanisms involved in the recovery phase of an infection are incompletely characterized at both the cellular and physiological levels. Here, we establish a Caenorhabditis elegans-Salmonella enterica model of acute infection and antibiotic treatment for studying biological changes during the resolution phase of an infection. Using whole genome expression profiles of acutely infected animals, we found that genes that are markers of innate immunity are down-regulated upon recovery, while genes involved in xenobiotic detoxification, redox regulation, and cellular homeostasis are up-regulated. In silico analyses demonstrated that genes altered during recovery from infection were transcriptionally regulated by conserved transcription factors, including GATA/ELT-2, FOXO/DAF-16, and Nrf/SKN-1. Finally, we found that recovery from an acute bacterial infection is dependent on ELT-2 activity.

Citing Articles

The Roles of Distinct Transcriptional Factors in the Innate Immunity of .

Afridi M, Tu H Cells. 2025; 14(5).

PMID: 40072056 PMC: 11899719. DOI: 10.3390/cells14050327.

Time-course swRNA-seq uncovers a hierarchical gene regulatory network in controlling the response-repair-remodeling after wounding.

Yu X, Zhou J, Ye W, Xu J, Li R, Huang L Commun Biol. 2024; 7(1):694.

PMID: 38844830 PMC: 11156874. DOI: 10.1038/s42003-024-06352-w.

The MAB-5/Hox family transcription factor is important for Caenorhabditis elegans innate immune response to Staphylococcus epidermidis infection.

Kywe C, Lundquist E, Ackley B, Lansdon P G3 (Bethesda). 2024; 14(5).

PMID: 38478633 PMC: 11075571. DOI: 10.1093/g3journal/jkae054.

Transcriptome profiling of the Caenorhabditis elegans intestine reveals that ELT-2 negatively and positively regulates intestinal gene expression within the context of a gene regulatory network.

Williams R, King D, Mastroianni I, Hill J, Apenes N, Ramirez G Genetics. 2023; 224(4).

PMID: 37183501 PMC: 10411582. DOI: 10.1093/genetics/iyad088.

Genomic and phenotypic profiling of Staphylococcus aureus isolates from bovine mastitis for antibiotic resistance and intestinal infectivity.

Majumder S, Sackey T, Viau C, Park S, Xia J, Ronholm J BMC Microbiol. 2023; 23(1):43.

PMID: 36803552 PMC: 9940407. DOI: 10.1186/s12866-023-02785-1.

References

Garsin D, Sifri C, Mylonakis E, Qin X, Singh K, Murray B . A simple model host for identifying Gram-positive virulence factors. Proc Natl Acad Sci U S A. 2001; 98(19):10892-7. PMC: 58570. DOI: 10.1073/pnas.191378698. View

Evans E, Kawli T, Tan M . Pseudomonas aeruginosa suppresses host immunity by activating the DAF-2 insulin-like signaling pathway in Caenorhabditis elegans. PLoS Pathog. 2008; 4(10):e1000175. PMC: 2568960. DOI: 10.1371/journal.ppat.1000175. View

Sem X, Rhen M . Pathogenicity of Salmonella enterica in Caenorhabditis elegans relies on disseminated oxidative stress in the infected host. PLoS One. 2012; 7(9):e45417. PMC: 3461013. DOI: 10.1371/journal.pone.0045417. View

Singh V, Aballay A . Endoplasmic reticulum stress pathway required for immune homeostasis is neurally controlled by arrestin-1. J Biol Chem. 2012; 287(40):33191-7. PMC: 3460425. DOI: 10.1074/jbc.M112.398362. View

Pukkila-Worley R, Ausubel F . Immune defense mechanisms in the Caenorhabditis elegans intestinal epithelium. Curr Opin Immunol. 2012; 24(1):3-9. PMC: 3660727. DOI: 10.1016/j.coi.2011.10.004. View

Tenor J, McCormick B, Ausubel F, Aballay A . Caenorhabditis elegans-based screen identifies Salmonella virulence factors required for conserved host-pathogen interactions. Curr Biol. 2004; 14(11):1018-24. DOI: 10.1016/j.cub.2004.05.050. View

Anyanful A, Easley K, Benian G, Kalman D . Conditioning protects C. elegans from lethal effects of enteropathogenic E. coli by activating genes that regulate lifespan and innate immunity. Cell Host Microbe. 2009; 5(5):450-62. PMC: 2992947. DOI: 10.1016/j.chom.2009.04.012. View

McGhee J . The C. elegans intestine. WormBook. 2007; :1-36. PMC: 4780959. DOI: 10.1895/wormbook.1.133.1. View

Troemel E, Chu S, Reinke V, Lee S, Ausubel F, Kim D . p38 MAPK regulates expression of immune response genes and contributes to longevity in C. elegans. PLoS Genet. 2006; 2(11):e183. PMC: 1635533. DOI: 10.1371/journal.pgen.0020183. View

10.

van der Hoeven R, McCallum K, Cruz M, Garsin D . Ce-Duox1/BLI-3 generated reactive oxygen species trigger protective SKN-1 activity via p38 MAPK signaling during infection in C. elegans. PLoS Pathog. 2012; 7(12):e1002453. PMC: 3245310. DOI: 10.1371/journal.ppat.1002453. View

11.

Kerry S, TeKippe M, Gaddis N, Aballay A . GATA transcription factor required for immunity to bacterial and fungal pathogens. PLoS One. 2006; 1:e77. PMC: 1762309. DOI: 10.1371/journal.pone.0000077. View

12.

Irazoqui J, Urbach J, Ausubel F . Evolution of host innate defence: insights from Caenorhabditis elegans and primitive invertebrates. Nat Rev Immunol. 2009; 10(1):47-58. PMC: 2965059. DOI: 10.1038/nri2689. View

13.

Reddy K, Andersen E, Kruglyak L, Kim D . A polymorphism in npr-1 is a behavioral determinant of pathogen susceptibility in C. elegans. Science. 2009; 323(5912):382-4. PMC: 2748219. DOI: 10.1126/science.1166527. View

14.

Means T, Aballay A . Models to study ancient host-pathogen interactions: lessons from Crete. EMBO Rep. 2010; 12(1):5-7. PMC: 3024139. DOI: 10.1038/embor.2010.205. View

15.

Huang D, Sherman B, Lempicki R . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4(1):44-57. DOI: 10.1038/nprot.2008.211. View

16.

Shore D, Ruvkun G . A cytoprotective perspective on longevity regulation. Trends Cell Biol. 2013; 23(9):409-20. PMC: 4057428. DOI: 10.1016/j.tcb.2013.04.007. View

17.

McGhee J, Sleumer M, Bilenky M, Wong K, McKay S, Goszczynski B . The ELT-2 GATA-factor and the global regulation of transcription in the C. elegans intestine. Dev Biol. 2006; 302(2):627-45. DOI: 10.1016/j.ydbio.2006.10.024. View

18.

Kawli T, Tan M . Neuroendocrine signals modulate the innate immunity of Caenorhabditis elegans through insulin signaling. Nat Immunol. 2008; 9(12):1415-24. DOI: 10.1038/ni.1672. View

19.

Partridge F, Gravato-Nobre M, Hodgkin J . Signal transduction pathways that function in both development and innate immunity. Dev Dyn. 2010; 239(5):1330-6. DOI: 10.1002/dvdy.22232. View

20.

McGhee J, Fukushige T, Krause M, Minnema S, Goszczynski B, Gaudet J . ELT-2 is the predominant transcription factor controlling differentiation and function of the C. elegans intestine, from embryo to adult. Dev Biol. 2008; 327(2):551-65. PMC: 2706090. DOI: 10.1016/j.ydbio.2008.11.034. View