A Polysaccharide Virulence Factor from Elicits Anti-inflammatory Effects through Induction of Interleukin-1 Receptor Antagonist


Aspergillus fumigatus is an opportunistic pathogenic fungus that primarily causes infections in the immunocompromised host. It is known that Aspergillus employs various strategies to evade immune recognition by the host's immune system. Recently, galactosaminogalactan (GAG), a new component of the Aspergillus cell wall, was discovered to have potent anti-inflammatory effects in mice making them more susceptible to Aspergillosis. In the current study we found that this anti-inflammatory property of GAG was due to its capacity to induce the potent anti-inflammatory cytokine interleukin-1 Receptor antagonist. This cytokine interferes with IL-1 signalling and thereby can reduce IL-1–induced immune responses such as T-cell responses. We also found that the induction of this anti-inflammatory cytokine by GAG correlates with increased fungal burden, and mice deficient for this cytokine were protected against aspergillosis. Additionally, we show that the capacity of GAG to induce the natural regulator of IL-1 signalling could be used in the treatment of IL-1–mediated disease such as allergy and colitis. Our study provides new insights on the immunoregulatory activity of GAG and opens up possibilities to exploit the anti-inflammatory potential of GAG as a therapy for inflammatory diseases.


Vyšlo v časopise: A Polysaccharide Virulence Factor from Elicits Anti-inflammatory Effects through Induction of Interleukin-1 Receptor Antagonist. PLoS Pathog 10(3): e32767. doi:10.1371/journal.ppat.1003936
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.ppat.1003936

Souhrn

Aspergillus fumigatus is an opportunistic pathogenic fungus that primarily causes infections in the immunocompromised host. It is known that Aspergillus employs various strategies to evade immune recognition by the host's immune system. Recently, galactosaminogalactan (GAG), a new component of the Aspergillus cell wall, was discovered to have potent anti-inflammatory effects in mice making them more susceptible to Aspergillosis. In the current study we found that this anti-inflammatory property of GAG was due to its capacity to induce the potent anti-inflammatory cytokine interleukin-1 Receptor antagonist. This cytokine interferes with IL-1 signalling and thereby can reduce IL-1–induced immune responses such as T-cell responses. We also found that the induction of this anti-inflammatory cytokine by GAG correlates with increased fungal burden, and mice deficient for this cytokine were protected against aspergillosis. Additionally, we show that the capacity of GAG to induce the natural regulator of IL-1 signalling could be used in the treatment of IL-1–mediated disease such as allergy and colitis. Our study provides new insights on the immunoregulatory activity of GAG and opens up possibilities to exploit the anti-inflammatory potential of GAG as a therapy for inflammatory diseases.


Zdroje

1. ChaiLY, HsuLY (2011) Recent advances in invasive pulmonary aspergillosis. Curr Opin Pulm Med 17: 160–166.

2. RomaniL (2011) Immunity to fungal infections. Nat Rev Immunol 11: 275–288.

3. ChaiLY, NeteaMG, VonkAG, KullbergBJ (2009) Fungal strategies for overcoming host innate immune response. Med Mycol 47: 227–236.

4. AimaniandaV, BayryJ, BozzaS, KniemeyerO, PerruccioK, et al. (2009) Surface hydrophobin prevents immune recognition of airborne fungal spores. Nature 460: 1117–1121.

5. ChaiLY, NeteaMG, SuguiJ, VonkAG, van de SandeWW, et al. (2010) Aspergillus fumigatus conidial melanin modulates host cytokine response. Immunobiology 215: 915–920.

6. ChaiLY, KullbergBJ, VonkAG, WarrisA, CambiA, et al. (2009) Modulation of Toll-like receptor 2 (TLR2) and TLR4 responses by Aspergillus fumigatus. Infect Immun 77: 2184–2192.

7. FontaineT, DelangleA, SimenelC, CoddevilleB, van VlietSJ, et al. (2011) Galactosaminogalactan, a new immunosuppressive polysaccharide of Aspergillus fumigatus. PLoS Pathog 7: e1002372.

8. LoussertC, SchmittC, PrevostMC, BalloyV, FadelE, et al. (2010) In vivo biofilm composition of Aspergillus fumigatus. Cell Microbiol 12: 405–410.

9. GravelatFN, BeauvaisA, LiuH, LeeMJ, SnarrBD, et al. (2013) Aspergillus Galactosaminogalactan Mediates Adherence to Host Constituents and Conceals Hyphal beta-Glucan from the Immune System. PLoS Pathog 9: e1003575.

10. SheppardDC (2011) Molecular mechanism of Aspergillus fumigatus adherence to host constituents. Curr Opin Microbiol 14: 375–379.

11. GuoL, WeiG, ZhuJ, LiaoW, LeonardWJ, et al. (2009) IL-1 family members and STAT activators induce cytokine production by Th2, Th17, and Th1 cells. Proc Natl Acad Sci U S A 106: 13463–13468.

12. Ben-SassonSZ, Hu-LiJ, QuielJ, CauchetauxS, RatnerM, et al. (2009) IL-1 acts directly on CD4 T cells to enhance their antigen-driven expansion and differentiation. Proc Natl Acad Sci U S A 106: 7119–7124.

13. DinarelloCA (2011) Interleukin-1 in the pathogenesis and treatment of inflammatory diseases. Blood 117: 3720–3732.

14. van de VeerdonkFL, NeteaMG, DinarelloCA, van der MeerJW (2011) Anakinra for the inflammatory complications of chronic granulomatous disease. Neth J Med 69: 95.

15. GrouxH, O′GarraA, BiglerM, RouleauM, AntonenkoS, et al. (1997) A CD4+ T-cell subset inhibits antigen-specific T-cell responses and prevents colitis. Nature 389: 737–742.

16. GlockerEO, KotlarzD, KleinC, ShahN, GrimbacherB (2011) IL-10 and IL-10 receptor defects in humans. Ann N Y Acad Sci 1246: 102–107.

17. van de VeerdonkFL, NeteaMG, DinarelloCA, JoostenLA (2011) Inflammasome activation and IL-1beta and IL-18 processing during infection. Trends Immunol 32: 110–116.

18. SainzJ, PerezE, Gomez-LoperaS, JuradoM (2008) IL1 gene cluster polymorphisms and its haplotypes may predict the risk to develop invasive pulmonary aspergillosis and modulate C-reactive protein level. J Clin Immunol 28: 473–485.

19. WernerJL, MetzAE, HornD, SchoebTR, HewittMM, et al. (2009) Requisite role for the dectin-1 beta-glucan receptor in pulmonary defense against Aspergillus fumigatus. J Immunol 182: 4938–4946.

20. MarrKA, CarterRA, BoeckhM, MartinP, CoreyL (2002) Invasive aspergillosis in allogeneic stem cell transplant recipients: changes in epidemiology and risk factors. Blood 100: 4358–4366.

21. SchaffnerA, DouglasH, BraudeA (1982) Selective protection against conidia by mononuclear and against mycelia by polymorphonuclear phagocytes in resistance to Aspergillus. Observations on these two lines of defense in vivo and in vitro with human and mouse phagocytes. J Clin Invest 69: 617–631.

22. KoendersMI, DevesaI, MarijnissenRJ, Abdollahi-RoodsazS, BootsAM, et al. (2008) Interleukin-1 drives pathogenic Th17 cells during spontaneous arthritis in interleukin-1 receptor antagonist-deficient mice. Arthritis Rheum 58: 3461–3470.

23. AksentijevichI, MastersSL, FergusonPJ, DanceyP, FrenkelJ, et al. (2009) An autoinflammatory disease with deficiency of the interleukin-1-receptor antagonist. N Engl J Med 360: 2426–2437.

24. LillyLM, GessnerMA, DunawayCW, MetzAE, SchwiebertL, et al. (2012) The beta-Glucan Receptor Dectin-1 Promotes Lung Immunopathology during Fungal Allergy via IL-22. J Immunol 189(7): 3653–60.

25. DinarelloCA, SimonA, van der MeerJW (2012) Treating inflammation by blocking interleukin-1 in a broad spectrum of diseases. Nat Rev Drug Discov 11: 633–652.

26. ChaiLY, van de VeerdonkF, MarijnissenRJ, ChengSC, KhooAL, et al. (2010) Anti-Aspergillus human host defence relies on type 1 T helper (Th1), rather than type 17 T helper (Th17), cellular immunity. Immunology 130: 46–54.

27. NeteaMG, WarrisA, Van der MeerJW, FentonMJ, Verver-JanssenTJ, et al. (2003) Aspergillus fumigatus evades immune recognition during germination through loss of toll-like receptor-4-mediated signal transduction. J Infect Dis 188: 320–326.

28. van de VeerdonkFL, MarijnissenRJ, KullbergBJ, KoenenHJ, ChengSC, et al. (2009) The macrophage mannose receptor induces IL-17 in response to Candida albicans. Cell Host Microbe 5: 329–340.

29. GearingAJ, BirdCR, BristowA, PooleS, ThorpeR (1987) A simple sensitive bioassay for interleukin-1 which is unresponsive to 10(3) U/ml of interleukin-2. J Immunol Methods 99: 7–11.

30. BonifaziP, D′AngeloC, ZagarellaS, ZelanteT, BozzaS, et al. (2010) Intranasally delivered siRNA targeting PI3K/Akt/mTOR inflammatory pathways protects from aspergillosis. Mucosal Immunol 3: 193–205.

31. BozzaS, PerruccioK, MontagnoliC, GazianoR, BellocchioS, et al. (2003) A dendritic cell vaccine against invasive aspergillosis in allogeneic hematopoietic transplantation. Blood 102: 3807–3814.

32. TakedatsuH, MichelsenKS, WeiB, LandersCJ, ThomasLS, et al. (2008) TL1A (TNFSF15) regulates the development of chronic colitis by modulating both T-helper 1 and T-helper 17 activation. Gastroenterology 135: 552–567.

33. EngelMA, LefflerA, NiedermirtlF, BabesA, ZimmermannK, et al. (2011) TRPA1 and substance P mediate colitis in mice. Gastroenterology 141: 1346–1358.

34. BellocchioS, MorettiS, PerruccioK, FallarinoF, BozzaS, et al. (2004) TLRs govern neutrophil activity in aspergillosis. J Immunol 173: 7406–7415.

35. YouY, RicherEJ, HuangT, BrodySL (2002) Growth and differentiation of mouse tracheal epithelial cells: selection of a proliferative population. Am J Physiol Lung Cell Mol Physiol 283: L1315–1321.

Štítky
Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

Článok vyšiel v časopise

PLOS Pathogens


2014 Číslo 3
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Eozinofilní granulomatóza s polyangiitidou
nový kurz

Betablokátory a Ca antagonisté z jiného úhlu
Autori: prof. MUDr. Michal Vrablík, Ph.D., MUDr. Petr Janský

Autori: doc. MUDr. Petr Čáp, Ph.D.

Farmakoterapie akutní a chronické bolesti

Získaná hemofilie - Povědomí o nemoci a její diagnostika

Všetky kurzy
Prihlásenie
Zabudnuté heslo

Nemáte účet?  Registrujte sa

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