随着免疫抑制人群的增多、检测技术的发展, 深部真菌感染日益受到人们的关注。真菌中的曲霉属成了这些免疫功能低下患者致病性感染的重要原因, 而烟曲霉在侵袭性曲
霉病例中最常见。侵袭力是烟曲霉菌极为重要的致病原因;病原菌侵入上皮、内皮细胞等组织细胞后才导致了可怕的侵袭性感染。从上世纪90 年代来, 对于侵袭的研究已逐步深
入, 为探讨复杂的致病机制打下了基础。侵袭性烟曲霉病一般的致病过程认为是烟曲霉孢子被宿主吸入下呼吸道, 侵入呼吸道上皮细胞后发育成菌丝, 菌丝进一步生长, 可侵入血管、进入血液, 造成全身播散[ 1] 。因此曲霉与宿主细胞( 上皮细胞、内皮细胞等) 的相互作用成了致病过程的重要环节。目前对病原体与宿主细胞作用的研究取得了一些进展, 对阐明致病机制、研究治疗靶点等有重要意义。
Citation： 徐小勇,施毅. Mechanisms of Aspergillus Fumigatus Invasion. Chinese Journal of Respiratory and Critical Care Medicine, 2010, 9(1): 94-96. doi: Copy
| 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.