Filarial nematodes maintain a mutualistic relationship with the endosymbiont Wolbachia. Depletion of Wolbachia produces profound defects in nematode development, fertility and viability and thus has great promise as a novel approach for treating filarial diseases. However, little is known concerning the basis for this mutualistic relationship. Here we demonstrate using whole mount confocal microscopy that an immediate response to Wolbachia depletion is extensive apoptosis in the adult germline, and in the somatic cells of the embryos, microfilariae and fourth-stage larvae (L4). Surprisingly, apoptosis occurs in the majority of embryonic cells that had not been infected prior to antibiotic treatment. In addition, no apoptosis occurs in the hypodermal chords, which are populated with large numbers of Wolbachia, although disruption of the hypodermal cytoskeleton occurs following their depletion. Thus, the induction of apoptosis upon Wolbachia depletion is non-cell autonomous and suggests the involvement of factors originating from Wolbachia in the hypodermal chords. The pattern of apoptosis correlates closely with the nematode tissues and processes initially perturbed following depletion of Wolbachia, embryogenesis and long-term sterilization, which are sustained for several months until the premature death of the adult worms. Our observations provide a cellular mechanism to account for the sustained reductions in microfilarial loads and interruption of transmission that occurs prior to macrofilaricidal activity following antibiotic therapy of filarial nematodes.
Vyšlo v časopise: Anti-filarial Activity of Antibiotic Therapy Is Due to Extensive Apoptosis after Depletion from Filarial Nematodes. PLoS Pathog 7(11): e32767. doi:10.1371/journal.ppat.1002351 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002351
1. KozekWJ 1977 Transovarially-transmitted intracellular microorganisms in adult and larval stages of Brugia malayi. J Parasitol 63 992 1000
2. KozekWJMarroquinHF 1977 Intracytoplasmic bacteria in Onchocerca volvulus. Am J Trop Med Hyg 26 663 678
3. TaylorMJHoeraufA 1999 Wolbachia bacteria of filarial nematodes. Parasitol Today 15 437 442
4. TaylorMJBiloKCrossHFArcherJPUnderwoodAP 1999 16S rDNA phylogeny and ultrastructural characterization of Wolbachia intracellular bacteria of the filarial nematodes Brugia malayi, B. pahangi, and Wuchereria bancrofti. Exp Parasitol 91 356 361
5. TaylorMJHoeraufABockarieM 2010 Lymphatic filariasis and onchocerciasis. Lancet 376 1175 1185
6. TownsonSHuttonDSiemienskaJHollickLScanlonT 2000 Antibiotics and Wolbachia in filarial nematodes: antifilarial activity of rifampicin, oxytetracycline and chloramphenicol against Onchocerca gutturosa, Onchocerca lienalis and Brugia pahangi. Ann Trop Med Parasit 94 801 816
7. TaylorMJBandiCHoeraufA 2005 Wolbachia bacterial endosymbionts of filarial nematodes. Adv Parasit 60 245 284
8. JohnstonKLWuBGuimaraesAFordLSlatkoBE 2010 Lipoprotein biosynthesis as a target for anti-Wolbachia treatment of filarial nematodes. Parasit Vectors 3 99
9. GavrieliYShermanYBen-SassonSA 1992 Identification of programmed cell death in situ via specific labeling of nuclear DNA fragmentation. J Cell Biol 119 493 501
10. SulstonJE 1988 The Nematode Caenorhabditis elegans. New York Cold Spring Harbor Lab. Press. NY
11. McGarryHFEgertonGLTaylorMJ 2004 Population dynamics of Wolbachia bacterial endosymbionts in Brugia malayi. Mol Biochem Parasit 135 57 67
12. LandmannFFosterJMSlatkoBSullivanW 2010 Asymmetric Wolbachia segregation during early Brugia malayi embryogenesis determines its distribution in adult host tissues. PLoS NTD 4 e758
13. TurnerJDTendongforNEsumMJohnstonKLLangleyRS 2010 Macrofilaricidal activity after doxycycline only treatment of Onchocerca volvulus in an area of Loa loa co-endemicity: a randomized controlled trial. PLoS NTD 4 e660
14. HoeraufAMandSVolkmannLButtnerMMarfo-DebrekyeiY 2003 Doxycycline in the treatment of human onchocerciasis: Kinetics of Wolbachia endobacteria reduction and of inhibition of embryogenesis in female Onchocerca worms. Microbes Infect 5 261 273
15. ArumugamSPfarrKMHoeraufA 2008 Infection of the intermediate mite host with Wolbachia-depleted Litomosoides sigmodontis microfilariae: impaired L1 to L3 development and subsequent sex-ratio distortion in adult worms. Int J Parasitol 38 981 987
16. SrivastavaKMisra-BhattacharyaS 2003 Tetracycline, a tool for transmission blocking of Brugia malayi in Mastomys coucha. Curr Sci 85 588 589
17. HoeraufANissen-PahleKHenkle-DuhrsenKBlaxterMLButtnerDW 1999 Tetracycline therapy targets intracellular bacteria in the filarial nematode Litomosoides sigmodontis and results in filarial infertility. J Clin Invest 103 11 18
18. SlatkoBETaylorMJFosterJM 2010 The Wolbachia endosymbiont as an anti-filarial nematode target. Symbiosis 51 55 65
19. FahertyCSMaurelliAT 2008 Staying alive: bacterial inhibition of apoptosis during infection. Trends Microbiol 16 173 180
20. RudelTKeppOKozjak-PavlovicV 2010 Interactions between bacterial pathogens and mitochondrial cell death pathways. Nat Rev Microbiol 8 693 705
21. RikihisaY 2010 Anaplasma phagocytophilum and Ehrlichia chaffeensis: subversive manipulators of host cells. Nat Rev Microbiol 8 328 339
22. HackerGFischerSF 2002 Bacterial anti-apoptotic activities. FEMS Microbiol Lett 211 1 6
23. JamesERGreenDR 2004 Manipulation of apoptosis in the host-parasite interaction. Trends Parasitol 20 280 287
24. FischerSFVierJKirschnekSKlosAHessS 2004 Chlamydia inhibit host cell apoptosis by degradation of proapoptotic BH3-only proteins. J Exp Med 200 905 916
25. NiuHKozjak-PavlovicVRudelTRikihisaY 2010 Anaplasma phagocytophilum Ats-1 is imported into host cell mitochondria and interferes with apoptosis induction. PLoS Path 6 e1000774
26. BazzocchiCComazziSSantoniRBandiCGenchiC 2007 Wolbachia surface protein (WSP) inhibits apoptosis in human neutrophils. Parasite Immunol 29 73 79
27. TurnerJDLangleyRSJohnstonKLGentilKFordL 2009 Wolbachia lipoprotein stimulates innate and adaptive immunity through Toll-like receptors 2 and 6 to induce disease manifestations of filariasis. J Biol Chem 284 22364 22378
28. PowerCPWangJHManningBKellMRAherneNJ 2004 Bacterial lipoprotein delays apoptosis in human neutrophils through inhibition of caspase-3 activity: regulatory roles for CD14 and TLR-2. J Immunol 173 5229 5237
29. PannebakkerBALoppinBElemansCPHumblotLVavreF 2007 Parasitic inhibition of cell death facilitates symbiosis. Proc Natl Acad Sci U S A 104 213 215
30. BrownlieJCCassBNRieglerMWitsenburgJJIturbe-OrmaetxeI 2009 Evidence for metabolic provisioning by a common invertebrate endosymbiont, Wolbachia pipientis, during periods of nutritional stress. PLoS Path 5 e1000368
31. KremerNVoroninDCharifDMavinguiPMollereauB 2009 Wolbachia interferes with ferritin expression and iron metabolism in insects. PLoS Path 5 e1000630
32. WuBNovelliJFosterJVaisvilaRConwayL 2009 The heme biosynthetic pathway of the obligate Wolbachia endosymbiont of Brugia malayi as a potential anti-filarial drug target. PLoS NTD 3 e475
33. FordLZhangJLiuJHashmiSFuhrmanJA 2009 Functional analysis of the cathepsin-like cysteine protease genes in adult Brugia malayi using RNA interference. PLoS NTD 3 e377
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