煙曲霉侵襲機制的研究_《中國呼吸與危重監護雜志》

作者：

徐小勇 , 施毅

南京軍區南京總醫院呼吸內科（江蘇南京 210002）通訊作者：施毅，E-mail shiyi56@126.com;

關鍵詞：

煙曲霉侵襲機制

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隨著免疫抑制人群的增多、檢測技術的發展, 深部真菌感染日益受到人們的關注。真菌中的曲霉屬成了這些免疫功能低下患者致病性感染的重要原因, 而煙曲霉在侵襲性曲
霉病例中最常見。侵襲力是煙曲霉菌極為重要的致病原因;病原菌侵入上皮、內皮細胞等組織細胞后才導致了可怕的侵襲性感染。從上世紀90 年代來, 對于侵襲的研究已逐步深
入, 為探討復雜的致病機制打下了基礎。侵襲性煙曲霉病一般的致病過程認為是煙曲霉孢子被宿主吸入下呼吸道, 侵入呼吸道上皮細胞后發育成菌絲, 菌絲進一步生長, 可侵入血管、進入血液, 造成全身播散[ 1] 。因此曲霉與宿主細胞( 上皮細胞、內皮細胞等) 的相互作用成了致病過程的重要環節。目前對病原體與宿主細胞作用的研究取得了一些進展, 對闡明致病機制、研究治療靶點等有重要意義。

引用本文： 徐小勇,施毅. 煙曲霉侵襲機制的研究. 中國呼吸與危重監護雜志, 2010, 9(1): 94-96. doi: 復制

1.	Filler SG,Sheppard DC.Fungal invasion of normally non-phagocytic host cells.PLoS Pathog,2006,2:e129.
2.	Sturtevant J,Latgé JP.Participation of complement in the phagocytosis of the conidia of Aspergillus fumigatus by human polymorphonuclear cells.J Infect Dis,1992,166:580-586.
3.	Rüchel R,Schaffrinski M.Versatile fluorescent staining of fungi in clinical specimens by using the optical brightener Blankophor.J Clin Microbiol,1999,37:2694-2696.
4.	Lopes Bezerra LM,Filler SG.Interactions of Aspergillus fumigatus with endothelial cells: internalization,injury,and stimulation of tissue factor activity.Blood,2004,103:2143-2149.
5.	Wasylnka JA,Moore MM.Uptake of Aspergillus fumigatus Conidia by phagocytic and nonphagocytic cells in vitro: quantitation using strains expressing green fluorescent protein.Infect Immun,2002,70:3156-3163.
6.	Luther K,Rohde M,Heesemann J,et al.Quantification of phagocytosis of Aspergillus conidia by macrophages using a novel antibody-independent assay.J Microbiol Methods,2006,66:170-173.
7.	Paris S,Boisvieux-Ulrich E,Crestani B,et al.Internalization of Aspergillus fumigatus conidia by epithelial and endothelial cells.Infect Immun,1997,65:1510-1514.
8.	Wang JE,Warris A,Ellingsen EA,et al.Involvement of CD14 and toll-like receptors in activation of human monocytes by Aspergillus fumigatus hyphae.Infect Immun,2001,69:2402-2406.
9.	Antachopoulos C,Roilides E.Cytokines and fungal infections.Br J Haematol,2005,129:583-596.
10.	Mambula SS,Sau K,Henneke P,et al.Toll-like receptor (TLR) signaling in response to Aspergillus fumigatus.J Biol Chem,2002,277:39320-39326.
11.	Meier A,Kirschning CJ,Nikolaus T,et al.Toll-like receptor (TLR) 2 and TLR4 are essential for Aspergillus-induced activation of murine macrophages.Cell Microbiol,2003,5:561-570.
12.	Netea MG,Azam T,Ferwerda G,et al.IL-32 synergizes with nucleotide oligomerization domain (NOD) 1 and NOD2 ligands for IL-1beta and IL-6 production through a caspase 1-dependent mechanism.Proc Natl Acad Sci U S A,2005,102:16309-16314.
13.	Bellocchio S,Moretti S,Perruccio K,et al.TLRs govern neutrophil activity in aspergillosis.J Immunol,2004,173:7406-7415.
14.	Chignard M,Balloy V,Sallenave JM,et al.Role of Toll-like receptors in lung innate defense against invasive aspergillosis.Distinct impact in immunocompetent and immunocompromized hosts.Clin Immunol,2007,124:238-243.
15.	Bellocchio S,Montagnoli C,Bozza S,et al.The contribution of the Toll-like/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo.J Immunol,2004,172:3059-3069.
16.	Bretz C,Gersuk G,Knoblaugh S,et al.MyD88 signaling contributes to early pulmonary responses to Aspergillus fumigatus.Infect Immun,2008,76:952-958.
17.	Bochud PY,Chien JW,Marr KA,et al.Toll-like receptor 4 polymorphisms and aspergillosis in stem-cell transplantation.N Engl J Med,2008,359:1766-1777.
18.	Balloy V,Si-Tahar M,Takeuchi O,et al.Involvement of toll-like receptor 2 in experimental invasive pulmonary aspergillosis.Infect Immun,2005,73:5420-5425.
19.	Hohl TM.Stage-specific innate immune recognition of Aspergillus fumigatus and modulation by echinocandin drugs.Med Mycol,2008,Apr 23:1-7.
20.	Steele C,Rapaka RR,Metz A,et al.The beta-glucan receptor dectin-1 recognizes specific morphologies of Aspergillus fumigatus.PLoS Pathog,2005,1:e42.
21.	Luther K,Torosantucci A,Brakhage AA,et al.Phagocytosis of Aspergillus fumigatus conidia by murine macrophages involves recognition by the dectin-1 beta-glucan receptor and Toll-like receptor 2.Cell Microbiol,2007,9:368-381.
22.	Bretz C,Gersuk G,Knoblaugh S,et al.MyD88 signaling contributes to early pulmonary responses to Aspergillus fumigatus.Infect Immun,2008,76:952-958.
23.	Toyotome T,Adachi Y,Watanabe A,et al.Activator protein 1 is triggered by Aspergillus fumigatus beta-glucans surface-exposed during specific growth stages.Microb Pathog,2008,44:141-150.
24.	Gersuk GM,Underhill DM,Zhu L,et al.Dectin-1 and TLRs permit macrophages to distinguish between different Aspergillus fumigatus cellular states.J Immunol,2006,176:3717-3724.
25.	Werner JL,Metz AE,Horn D,et al.Requisite role for the dectin-1 beta-glucan receptor in pulmonary defense against Aspergillus fumigatus.J Immunol,2009,182:4938-4946.
26.	Bals R,Hiemstra PS.Innate immunity in the lung: how epithelial cells fight against respiratory pathogens.Eur Respir J,2004,23:327-333.
27.	Balloy V,Sallenave JM,Wu Y,et al.Aspergillus fumigatus-induced interleukin-8 synthesis by respiratory epithelial cells is controlled by the phosphatidylinositol 3-kinase,p38 MAPK,and ERK1/2 pathways and not by the toll-like receptor-MyD88 pathway.J Biol Chem,2008,283:30513-30521.
28.	Bellanger AP,Millon L,Khoufache K,et al.Aspergillus fumigatus germ tube growth and not conidia ingestion induces expression of inflammatory mediator genes in the human lung epithelial cell line A549.J Med Microbiol,2009,58(Pt 2):174-179.
29.	Alekseeva L,Huet D,Féménia F,et al.Inducible expression of beta defensins by human respiratory epithelial cells exposed to Aspergillus fumigatus organisms.BMC Microbiol,2009,9:33.
30.	Féménia F,Huet D,Lair-Fulleringer S,et al.Effects of conidia of various Aspergillus species on apoptosis of human pneumocytes and bronchial epithelial cells.Mycopathologia,2009,167:249-262.
31.	Chiang LY,Sheppard DC,Gravelat FN,et al.Aspergillus fumigatus stimulates leukocyte adhesion molecules and cytokine production by endothelial cells in vitro and during invasive pulmonary disease.Infect Immun,2008,76:3429-3438.
32.	Kamai Y,Lossinsky AS,Liu H,et al.Polarized response of endothelial cells to invasion by Aspergillus fumigatus.Cell Microbiol,2009,11:170-182.
33.	Phan QT,Myers CL,Fu Y,et al.Als3 is a Candida albicans invasin that binds to cadherins and induces endocytosis by host cells.PLoS Biol,2007,5:e64.
34.	Phan QT,Fratti RA,Prasadarao NV,et al N-cadherin mediates endocytosis of Candida albicans by endothelial cells.J Biol Chem,2005,280:10455-10461.

1. Filler SG,Sheppard DC.Fungal invasion of normally non-phagocytic host cells.PLoS Pathog,2006,2:e129.
2. Sturtevant J,Latgé JP.Participation of complement in the phagocytosis of the conidia of Aspergillus fumigatus by human polymorphonuclear cells.J Infect Dis,1992,166:580-586.
3. Rüchel R,Schaffrinski M.Versatile fluorescent staining of fungi in clinical specimens by using the optical brightener Blankophor.J Clin Microbiol,1999,37:2694-2696.
4. Lopes Bezerra LM,Filler SG.Interactions of Aspergillus fumigatus with endothelial cells: internalization,injury,and stimulation of tissue factor activity.Blood,2004,103:2143-2149.
5. Wasylnka JA,Moore MM.Uptake of Aspergillus fumigatus Conidia by phagocytic and nonphagocytic cells in vitro: quantitation using strains expressing green fluorescent protein.Infect Immun,2002,70:3156-3163.
6. Luther K,Rohde M,Heesemann J,et al.Quantification of phagocytosis of Aspergillus conidia by macrophages using a novel antibody-independent assay.J Microbiol Methods,2006,66:170-173.
7. Paris S,Boisvieux-Ulrich E,Crestani B,et al.Internalization of Aspergillus fumigatus conidia by epithelial and endothelial cells.Infect Immun,1997,65:1510-1514.
8. Wang JE,Warris A,Ellingsen EA,et al.Involvement of CD14 and toll-like receptors in activation of human monocytes by Aspergillus fumigatus hyphae.Infect Immun,2001,69:2402-2406.
9. Antachopoulos C,Roilides E.Cytokines and fungal infections.Br J Haematol,2005,129:583-596.
10. Mambula SS,Sau K,Henneke P,et al.Toll-like receptor (TLR) signaling in response to Aspergillus fumigatus.J Biol Chem,2002,277:39320-39326.
11. Meier A,Kirschning CJ,Nikolaus T,et al.Toll-like receptor (TLR) 2 and TLR4 are essential for Aspergillus-induced activation of murine macrophages.Cell Microbiol,2003,5:561-570.
12. Netea MG,Azam T,Ferwerda G,et al.IL-32 synergizes with nucleotide oligomerization domain (NOD) 1 and NOD2 ligands for IL-1beta and IL-6 production through a caspase 1-dependent mechanism.Proc Natl Acad Sci U S A,2005,102:16309-16314.
13. Bellocchio S,Moretti S,Perruccio K,et al.TLRs govern neutrophil activity in aspergillosis.J Immunol,2004,173:7406-7415.
14. Chignard M,Balloy V,Sallenave JM,et al.Role of Toll-like receptors in lung innate defense against invasive aspergillosis.Distinct impact in immunocompetent and immunocompromized hosts.Clin Immunol,2007,124:238-243.
15. Bellocchio S,Montagnoli C,Bozza S,et al.The contribution of the Toll-like/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo.J Immunol,2004,172:3059-3069.
16. Bretz C,Gersuk G,Knoblaugh S,et al.MyD88 signaling contributes to early pulmonary responses to Aspergillus fumigatus.Infect Immun,2008,76:952-958.
17. Bochud PY,Chien JW,Marr KA,et al.Toll-like receptor 4 polymorphisms and aspergillosis in stem-cell transplantation.N Engl J Med,2008,359:1766-1777.
18. Balloy V,Si-Tahar M,Takeuchi O,et al.Involvement of toll-like receptor 2 in experimental invasive pulmonary aspergillosis.Infect Immun,2005,73:5420-5425.
19. Hohl TM.Stage-specific innate immune recognition of Aspergillus fumigatus and modulation by echinocandin drugs.Med Mycol,2008,Apr 23:1-7.
20. Steele C,Rapaka RR,Metz A,et al.The beta-glucan receptor dectin-1 recognizes specific morphologies of Aspergillus fumigatus.PLoS Pathog,2005,1:e42.
21. Luther K,Torosantucci A,Brakhage AA,et al.Phagocytosis of Aspergillus fumigatus conidia by murine macrophages involves recognition by the dectin-1 beta-glucan receptor and Toll-like receptor 2.Cell Microbiol,2007,9:368-381.
22. Bretz C,Gersuk G,Knoblaugh S,et al.MyD88 signaling contributes to early pulmonary responses to Aspergillus fumigatus.Infect Immun,2008,76:952-958.
23. Toyotome T,Adachi Y,Watanabe A,et al.Activator protein 1 is triggered by Aspergillus fumigatus beta-glucans surface-exposed during specific growth stages.Microb Pathog,2008,44:141-150.
24. Gersuk GM,Underhill DM,Zhu L,et al.Dectin-1 and TLRs permit macrophages to distinguish between different Aspergillus fumigatus cellular states.J Immunol,2006,176:3717-3724.
25. Werner JL,Metz AE,Horn D,et al.Requisite role for the dectin-1 beta-glucan receptor in pulmonary defense against Aspergillus fumigatus.J Immunol,2009,182:4938-4946.
26. Bals R,Hiemstra PS.Innate immunity in the lung: how epithelial cells fight against respiratory pathogens.Eur Respir J,2004,23:327-333.
27. Balloy V,Sallenave JM,Wu Y,et al.Aspergillus fumigatus-induced interleukin-8 synthesis by respiratory epithelial cells is controlled by the phosphatidylinositol 3-kinase,p38 MAPK,and ERK1/2 pathways and not by the toll-like receptor-MyD88 pathway.J Biol Chem,2008,283:30513-30521.
28. Bellanger AP,Millon L,Khoufache K,et al.Aspergillus fumigatus germ tube growth and not conidia ingestion induces expression of inflammatory mediator genes in the human lung epithelial cell line A549.J Med Microbiol,2009,58(Pt 2):174-179.
29. Alekseeva L,Huet D,Féménia F,et al.Inducible expression of beta defensins by human respiratory epithelial cells exposed to Aspergillus fumigatus organisms.BMC Microbiol,2009,9:33.
30. Féménia F,Huet D,Lair-Fulleringer S,et al.Effects of conidia of various Aspergillus species on apoptosis of human pneumocytes and bronchial epithelial cells.Mycopathologia,2009,167:249-262.
31. Chiang LY,Sheppard DC,Gravelat FN,et al.Aspergillus fumigatus stimulates leukocyte adhesion molecules and cytokine production by endothelial cells in vitro and during invasive pulmonary disease.Infect Immun,2008,76:3429-3438.
32. Kamai Y,Lossinsky AS,Liu H,et al.Polarized response of endothelial cells to invasion by Aspergillus fumigatus.Cell Microbiol,2009,11:170-182.
33. Phan QT,Myers CL,Fu Y,et al.Als3 is a Candida albicans invasin that binds to cadherins and induces endocytosis by host cells.PLoS Biol,2007,5:e64.
34. Phan QT,Fratti RA,Prasadarao NV,et al N-cadherin mediates endocytosis of Candida albicans by endothelial cells.J Biol Chem,2005,280:10455-10461.

《中國呼吸與危重監護雜志》

煙曲霉侵襲機制的研究

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《中國呼吸與危重監護雜志》

煙曲霉侵襲機制的研究

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