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. 2013 May 18;4(7):529–538. doi: 10.1007/s13238-013-2127-9

Human pathogenic fungus Trichophyton schoenleinii activates the NLRP3 inflammasome

Hua Li 12127,22127, Shuxian Wu 22127,, Liming Mao 22127,, Guowei Lei 12127,22127, Liping Zhang 32127, Ailing Lu 22127, Liguo An 12127, Guiwen Yang 12127, Paride Abliz 32127,, Guangxun Meng 22127,
PMCID: PMC4875508  PMID: 23686720

Abstract

The fungus Trichophyton schoenleinii (T. schoenleinii) is the causative agent of Trichophytosis and Tinea favosa of the scalp in certain regions of Eurasia and Africa. Human innate immune system plays an important role in combating with various pathogens including fungi. The inflammasome is one of the most critical arms of host innate immunity, which is a protein complex controlling maturation of IL-1β. To clarify whether T. schoenleinii is able to activate the inflammasome, we analyzed human monocytic cell line THP-1 for IL-1β production upon infection with T. schoenleinii strain isolated from Tinea favosa patients, and rapid IL-1β secretion from THP-1 cells was observed. Moreover, applying competitive inhibitors and gene specific silencing with shRNA, we found that T. schoenleinii induced IL-1β secretion, ASC pyroptosome formation as well as caspase-1 activation were all dependent on NLRP3. Cathepsin B activity, ROS production and K+ efflux were required for the inflammasome activation by T. schoenleinii. Our data thus reveal that the NLRP3 inflammasome plays an important role in host defense against T. schoenleinii, and suggest that manipulating NLRP3 signaling can be a novel approach for control of diseases caused by T. schoenleinii infection.

Keywords: innate immunity, inflammasome, NLRP3, Trichophyton schoenleinii, infection

Footnotes

These authors contributed equally to this work.

Contributor Information

Paride Abliz, Email: palidaa@yahoo.com.cn.

Guangxun Meng, Email: gxmeng@sibs.ac.cn.

References

  1. Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006;124:783–801. doi: 10.1016/j.cell.2006.02.015. [DOI] [PubMed] [Google Scholar]
  2. Allen IC, Scull MA, Moore CB, Holl EK, McElvania-TeKippe E, Taxman DJ, Guthrie EH, Pickles RJ, Ting JP. The NLRP3 inflammasome mediates in vivo innate immunity to influenza A virus through recognition of viral RNA. Immunity. 2009;30:556–565. doi: 10.1016/j.immuni.2009.02.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bauernfeind F, Bartok E, Rieger A, Franchi L, Nunez G, Hornung V. Cutting edge: reactive oxygen species inhibitors block priming, but not activation, of the NLRP3 inflammasome. J Immunol. 2011;187:613–617. doi: 10.4049/jimmunol.1100613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bauernfeind F, Bartok E, Rieger A, Franchi L, Nunez G, Hornung V. Cutting edge: reactive oxygen species inhibitors block priming, but not activation, of the NLRP3 inflammasome. J Immunol. 2011;187:613–617. doi: 10.4049/jimmunol.1100613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bretz C, Gersuk G, Knoblaugh S, Chaudhary N, Randolph-Habecker J, Hackman RC, Staab J, Marr KA. MyD88 signaling contributes to early pulmonary responses to Aspergillus fumigatus. Infect Immun. 2008;76:952–958. doi: 10.1128/IAI.00927-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bugarcic A, Hitchens K, Beckhouse AG, Wells CA, Ashman RB, Blanchard H. Human and mouse macrophage-inducible C-type lectin (Mincle) bind Candida albicans. Glycobiology. 2008;18:679–685. doi: 10.1093/glycob/cwn046. [DOI] [PubMed] [Google Scholar]
  7. Dinarello CA, Simon A, van der Meer JW. Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov. 2012;11:633–652. doi: 10.1038/nrd3800. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fernandes-Alnemri T, Alnemri ES. Assembly, purification, and assay of the activity of the ASC pyroptosome. Methods Enzymol. 2008;442:251–270. doi: 10.1016/S0076-6879(08)01413-4. [DOI] [PubMed] [Google Scholar]
  9. Fernandes-Alnemri T, Wu J, Yu JW, Datta P, Miller B, Jankowski W, Rosenberg S, Zhang J, Alnemri ES. The pyroptosome: a supramolecular assembly of ASC dimers mediating inflammatory cell death via caspase-1 activation. Cell Death Differ. 2007;14:1590–1604. doi: 10.1038/sj.cdd.4402194. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Franchi L, Eigenbrod T, Munoz-Planillo R, Nunez G. The inflammasome: a caspase-1-activation platform that regulates immune responses and disease pathogenesis. Nat Immunol. 2009;10:241–247. doi: 10.1038/ni.1703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Gersuk GM, Underhill DM, Zhu L, Marr KA. Dectin-1 and TLRs permit macrophages to distinguish between different Aspergillus fumigatus cellular states. J Immunol. 2006;176:3717–3724. doi: 10.4049/jimmunol.176.6.3717. [DOI] [PubMed] [Google Scholar]
  12. Gross O, Poeck H, Bscheider M, Dostert C, Hannesschlager N, Endres S, Hartmann G, Tardivel A, Schweighoffer E, Tybulewicz V, et al. Syk kinase signalling couples to the Nlrp3 inflammasome for anti-fungal host defence. Nature. 2009;459:433–436. doi: 10.1038/nature07965. [DOI] [PubMed] [Google Scholar]
  13. Ha SD, Martins A, Khazaie K, Han J, Chan BM, Kim SO. Cathepsin B is involved in the trafficking of TNF-alphacontaining vesicles to the plasma membrane in macrophages. J Immunol. 2008;181:690–697. doi: 10.4049/jimmunol.181.1.690. [DOI] [PubMed] [Google Scholar]
  14. Hardison SE, Brown GD. C-type lectin receptors orchestrate antifungal immunity. Nat Immunol. 2012;13:817–822. doi: 10.1038/ni.2369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hise AG, Tomalka J, Ganesan S, Patel K, Hall BA, Brown GD, Fitzgerald KA. An essential role for the NLRP3 inflammasome in host defense against the human fungal pathogen Candida albicans. Cell Host Microbe. 2009;5:487–497. doi: 10.1016/j.chom.2009.05.002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hohl TM, Van Epps HL, Rivera A, Morgan LA, Chen PL, Feldmesser M, Pamer EG. Aspergillus fumigatus triggers inflammatory responses by stage-specific beta-glucan display. PLoS Pathog. 2005;1:e30. doi: 10.1371/journal.ppat.0010030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Juliana C, Fernandes-Alnemri T, Wu J, Datta P, Solorzano L, Yu JW, Meng R, Quong AA, Latz E, Scott CP, et al. Antiinflammatory compounds parthenolide and Bay 11-7082 are direct inhibitors of the inflammasome. J Biol Chem. 2010;285:9792–9802. doi: 10.1074/jbc.M109.082305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kankkunen P, Teirila L, Rintahaka J, Alenius H, Wolff H, Matikainen S. (1,3)-beta-glucans activate both dectin-1 and NLRP3 inflammasome in human macrophages. J Immunol. 2010;184:6335–6342. doi: 10.4049/jimmunol.0903019. [DOI] [PubMed] [Google Scholar]
  19. Keller M, Ruegg A, Werner S, Beer HD. Active caspase-1 is a regulator of unconventional protein secretion. Cell. 2008;132:818–831. doi: 10.1016/j.cell.2007.12.040. [DOI] [PubMed] [Google Scholar]
  20. Martinon F, Burns K, Tschopp J. The inflammasome: a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta. Mol Cell. 2002;10:417–426. doi: 10.1016/S1097-2765(02)00599-3. [DOI] [PubMed] [Google Scholar]
  21. Naldini L, Blomer U, Gallay P, Ory D, Mulligan R, Gage FH, Verma IM, Trono D. In vivo gene delivery and stable transduction of nondividing cells by a lentiviral vector. Science. 1996;272:263–267. doi: 10.1126/science.272.5259.263. [DOI] [PubMed] [Google Scholar]
  22. Petrilli V, Papin S, Dostert C, Mayor A, Martinon F, Tschopp J. Activation of the NALP3 inflammasome is triggered by low intracellular potassium concentration. Cell Death Differ. 2007;14:1583–1589. doi: 10.1038/sj.cdd.4402195. [DOI] [PubMed] [Google Scholar]
  23. Pierini R, Juruj C, Perret M, Jones CL, Mangeot P, Weiss DS, Henry T. AIM2/ASC triggers caspase-8-dependent apoptosis in Francisella-infected caspase-1-deficient macrophages. Cell Death Differ. 2012;19:1709–1721. doi: 10.1038/cdd.2012.51. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Said-Sadier N, Padilla E, Langsley G, Ojcius DM. Aspergillus fumigatus stimulates the NLRP3 inflammasome through a pathway requiring ROS production and the Syktyrosine kinase. PLoS One. 2010;5:e10008. doi: 10.1371/journal.pone.0010008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Schroder K, Zhou R, Tschopp J. The NLRP3 inflammasome: a sensor for metabolic danger? Science. 2010;327:296–300. doi: 10.1126/science.1184003. [DOI] [PubMed] [Google Scholar]
  26. Tai SL, Tian SR, Dong YR. Survey report of pathogens of tinea capitis in Xinjiang. China J Derm Veneral. 1992;6:218. [Google Scholar]
  27. Tschopp J, Schroder K. NLRP3 inflammasome activation: The convergence of multiple signalling pathways on ROS production? Nat Rev Immunol. 2010;10:210–215. doi: 10.1038/nri2725. [DOI] [PubMed] [Google Scholar]
  28. Twig G, Elorza A, Molina AJ, Mohamed H, Wikstrom JD, Walzer G, Stiles L, Haigh SE, Katz S, Las G, et al. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J. 2008;27:433–446. doi: 10.1038/sj.emboj.7601963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Werner JL, Metz AE, Horn D, Schoeb TR, Hewitt MM, Schwiebert LM, Faro-Trindade I, Brown GD, Steele C. Requisite role for the dectin-1 beta-glucan receptor in pulmonary defense against Aspergillus fumigatus. J Immunol. 2009;182:4938–4946. doi: 10.4049/jimmunol.0804250. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Yamasaki S, Ishikawa E, Sakuma M, Hara H, Ogata K, Saito T. Mincle is an ITAM-coupled activating receptor that senses damaged cells. Nat Immunol. 2008;9:1179–1188. doi: 10.1038/ni.1651. [DOI] [PubMed] [Google Scholar]

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