#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

A Decline in p38 MAPK Signaling Underlies Immunosenescence in


The decline in immune function with aging, known as immunosenescence, has been implicated in evolutionarily diverse species, but the underlying molecular mechanisms are not understood. During aging in Caenorhabditis elegans, intestinal tissue deterioration and the increased intestinal proliferation of bacteria are observed, but how innate immunity changes during C. elegans aging has not been defined. Here we show that C. elegans exhibits increased susceptibility to bacterial infection with age, and we establish that aging is associated with a decline in the activity of the conserved PMK-1 p38 mitogen-activated protein kinase pathway, which regulates innate immunity in C. elegans. Our data define the phenomenon of innate immunosenescence in C. elegans in terms of the age-dependent dynamics of the PMK-1 innate immune signaling pathway, and they suggest that a cycle of intestinal tissue aging, immunosenescence, and bacterial proliferation leads to death in aging C. elegans.


Vyšlo v časopise: A Decline in p38 MAPK Signaling Underlies Immunosenescence in. PLoS Genet 7(5): e32767. doi:10.1371/journal.pgen.1002082
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002082

Souhrn

The decline in immune function with aging, known as immunosenescence, has been implicated in evolutionarily diverse species, but the underlying molecular mechanisms are not understood. During aging in Caenorhabditis elegans, intestinal tissue deterioration and the increased intestinal proliferation of bacteria are observed, but how innate immunity changes during C. elegans aging has not been defined. Here we show that C. elegans exhibits increased susceptibility to bacterial infection with age, and we establish that aging is associated with a decline in the activity of the conserved PMK-1 p38 mitogen-activated protein kinase pathway, which regulates innate immunity in C. elegans. Our data define the phenomenon of innate immunosenescence in C. elegans in terms of the age-dependent dynamics of the PMK-1 innate immune signaling pathway, and they suggest that a cycle of intestinal tissue aging, immunosenescence, and bacterial proliferation leads to death in aging C. elegans.


Zdroje

1. ShanleyDPAwDManleyNRPalmerDB 2009 An evolutionary perspective on the mechanisms of immunosenescence. Trends Immunol 30 374 381

2. PandaAArjonaASapeyEBaiFFikrigE 2009 Human innate immunosenescence: causes and consequences for immunity in old age. Trends Immunol 30 325 333

3. FranceschiCCapriMMontiDGiuntaSOlivieriF 2007 Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 128 92 105

4. KongKFDelrouxKWangXQianFArjonaA 2008 Dysregulation of TLR3 impairs the innate immune response to West Nile virus in the elderly. J Virol 82 7613 7623

5. ZerofskyMHarelESilvermanNTatarM 2005 Aging of the innate immune response in Drosophila melanogaster. Aging Cell 4 103 108

6. RamsdenSCheungYYSeroudeL 2008 Functional analysis of the Drosophila immune response during aging. Aging Cell 7 225 236

7. GariganDHsuALFraserAGKamathRSAhringerJ 2002 Genetic analysis of tissue aging in Caenorhabditis elegans: a role for heat-shock factor and bacterial proliferation. Genetics 161 1101 1112

8. HerndonLASchmeissnerPJDudaronekJMBrownPAListnerKM 2002 Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans. Nature 419 808 814

9. GemsDRiddleDL 2000 Genetic, behavioral and environmental determinants of male longevity in Caenorhabditis elegans. Genetics 154 1597 1610

10. KimDHFeinbaumRAlloingGEmersonFEGarsinDA 2002 A conserved p38 MAP kinase pathway in Caenorhabditis elegans innate immunity. Science 297 623 626

11. PujolNCypowyjSZieglerKMilletAAstrainA 2008 Distinct innate immune responses to infection and wounding in the C. elegans epidermis. Curr Biol 18 481 489

12. ShiversRPPaganoDJKooistraTRichardsonCEReddyKC 2010 Phosphorylation of the conserved transcription factor ATF-7 by PMK-1 p38 MAPK regulates innate immunity in Caenorhabditis elegans. PLoS Genet 6 e1000892 doi:10.1371/journal.pgen.1000892

13. TroemelERChuSWReinkeVLeeSSAusubelFM 2006 p38 MAPK regulates expression of immune response genes and contributes to longevity in C. elegans. PLoS Genet 2 e183 doi:10.1371/journal.pgen.0020183

14. ShiversRPYoungmanMJKimDH 2008 Transcriptional responses to pathogens in Caenorhabditis elegans. Curr Opin Microbiol 11 251 256

15. TanMWMahajan-MiklosSAusubelFM 1999 Killing of Caenorhabditis elegans by Pseudomonas aeruginosa used to model mammalian bacterial pathogenesis. Proc Natl Acad Sci U S A 96 715 720

16. KurzCLEwbankJJ 2003 Caenorhabditis elegans: an emerging genetic model for the study of innate immunity. Nat Rev Genet 4 380 390

17. LawsTRHardingSVSmithMPAtkinsTPTitballRW 2004 Age influences resistance of Caenorhabditis elegans to killing by pathogenic bacteria. FEMS Microbiol Lett 234 281 287

18. LundJTedescoPDukeKWangJKimSK 2002 Transcriptional profile of aging in C. elegans. Curr Biol 12 1566 1573

19. BudovskayaYVWuKSouthworthLKJiangMTedescoP 2008 An elt-3/elt-5/elt-6 GATA transcription circuit guides aging in C. elegans. Cell 134 291 303

20. WongDBazopoulouDPujolNTavernarakisNEwbankJJ 2007 Genome-wide investigation reveals pathogen-specific and shared signatures in the response of Caenorhabditis elegans to infection. Genome Biol 8 R194

21. SchulenburgHEwbankJJ 2007 The genetics of pathogen avoidance in Caenorhabditis elegans. Mol Microbiol 66 563 570

22. MurphyCTMcCarrollSABargmannCIFraserAKamathRS 2003 Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans. Nature 424 277 283

23. McElweeJJSchusterEBlancEThomasJHGemsD 2004 Shared transcriptional signature in Caenorhabditis elegans Dauer larvae and long-lived daf-2 mutants implicates detoxification system in longevity assurance. J Biol Chem 279 44533 44543

24. McGheeJDSleumerMCBilenkyMWongKMcKaySJ 2007 The ELT-2 GATA-factor and the global regulation of transcription in the C. elegans intestine. Dev Biol 302 627 645

25. PauliFLiuYKimYAChenPJKimSK 2006 Chromosomal clustering and GATA transcriptional regulation of intestine-expressed genes in C. elegans. Development 133 287 295

26. KimDHLiberatiNTMizunoTInoueHHisamotoN 2004 Integration of Caenorhabditis elegans MAPK pathways mediating immunity and stress resistance by MEK-1 MAPK kinase and VHP-1 MAPK phosphatase. Proc Natl Acad Sci U S A 101 10990 10994

27. GarsinDASifriCDMylonakisEQinXSinghKV 2001 A simple model host for identifying Gram-positive virulence factors. Proc Natl Acad Sci U S A 98 10892 10897

28. LibinaNBermanJRKenyonC 2003 Tissue-specific activities of C. elegans DAF-16 in the regulation of lifespan. Cell 115 489 502

29. ApfeldJKenyonC 1998 Cell nonautonomy of C. elegans daf-2 function in the regulation of diapause and life span. Cell 95 199 210

30. WolkowCAKimuraKDLeeMSRuvkunG 2000 Regulation of C. elegans life-span by insulinlike signaling in the nervous system. Science 290 147 150

31. MurphyCTLeeSJKenyonC 2007 Tissue entrainment by feedback regulation of insulin gene expression in the endoderm of Caenorhabditis elegans. Proc Natl Acad Sci U S A 104 19046 19050

32. KogaMZwaalRGuanKLAveryLOhshimaY 2000 A Caenorhabditis elegans MAP kinase kinase, MEK-1, is involved in stress responses. Embo J 19 5148 5156

33. RussellJA 2006 Management of sepsis. N Engl J Med 355 1699 1713

34. RichardsonCEKooistraTKimDH 2010 An essential role for XBP-1 in host protection against immune activation in C. elegans. Nature 463 1092 1095

35. HoogewijsDHouthoofdKMatthijssensFVandesompeleJVanfleterenJR 2008 Selection and validation of a set of reliable reference genes for quantitative sod gene expression analysis in C. elegans. BMC Mol Biol 9 9

36. PocockRHobertO 2008 Oxygen levels affect axon guidance and neuronal migration in Caenorhabditis elegans. Nat Neurosci 11 894 900

37. WuZIrizarryRA 2004 Preprocessing of oligonucleotide array data. Nat Biotechnol 22 656 658; author reply, 658

38. Al-ShahrourFMinguezPVaquerizasJMCondeLDopazoJ 2005 BABELOMICS: a suite of web tools for functional annotation and analysis of groups of genes in high-throughput experiments. Nucleic Acids Res 33 W460 464

39. KamathRSFraserAGDongYPoulinGDurbinR 2003 Systematic functional analysis of the Caenorhabditis elegans genome using RNAi. Nature 421 231 237

40. TimmonsLCourtDLFireA 2001 Ingestion of bacterially expressed dsRNAs can produce specific and potent genetic interference in Caenorhabditis elegans. Gene 263 103 112

Štítky
Genetika Reprodukčná medicína

Článok vyšiel v časopise

PLOS Genetics


2011 Číslo 5
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz

Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#