宿主抗曲霉菌感染免疫机制的研究进展

摘要/Abstract

摘要： 随着广谱抗生素、糖皮质激素和免疫抑制剂的广泛应用,艾滋病、糖尿病等疾病的发病率不断上升,免疫受损患者日益增多,侵袭性曲霉菌感染逐渐增加,并越来越受到关注。阐明曲霉菌感染的发病机制,从而找到有效的治疗手段是基础研究和临床工作者的共同命题。宿主的免疫对于曲霉菌感染的发病机制具有至关重要的作用,掌握宿主对曲霉菌的免疫机制是研究曲霉菌感染的基础,该文就宿主对曲霉菌感染免疫机制的研究进展作一综述。

关键词: 曲霉菌, 侵袭性曲霉病, 免疫机制, 真菌

Abstract: With the wide use of broad-spectrum antibiotics, corticosteroids and immunosuppressive drugs, and the rising incidence of AIDS, diabetes etc, the number of immunocompromised patient is increasing. Follow this, invasive Aspergillus infections are increasing gradually and more attentive than before. To clarify the pathogenesis and find the effective treatment of Aspergillus infections are the common propositions for basic researches and clinical workers. Host's immunity plays an important role in the pathogenesis of Aspergillus infection.To master host's immune mechanisms of Aspergillus is the foundation of studying Aspergillus infection. In our article, progresses on the study of host's immune mechanisms against Aspergillus infections are reviewed.

Key words: Aspergillus, invasive aspergillosis, immune mechanism, fungus

中图分类号:

R379.6

阎玉彦, 赵作涛, 刘红刚. 宿主抗曲霉菌感染免疫机制的研究进展[J]. 中国真菌学杂志, 2013, 8(5): 302-306.

YAN Yu-yan, ZHAO Zuo-tao, LIU Hong-gang. Research progress of host’s immune mechanism to resist Aspergillus infection[J]. Chinese Journal of Mycology, 2013, 8(5): 302-306.

参考文献

[1] Romani L. Immunity to fungal infections[J]. Nature reviews, 2004, 4(1):1-13.
[2] Roeder A, Kirschning CJ, Rupec RA, et al. Toll-like receptors and innate antifungal responses[J]. Trends Microbiol, 2004, 12(1):44-49.
[3] Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity[J]. Cell, 2006, 124(4):783-801.
[4] Wang JE, Warris A, Ellingsen EA, et al. Involvement of CD14 and Toll-like receptors in activation of human monocytes by Aspergillus fumigatus hyphae[J]. Infect Immun, 2001, 69(4):2402-2406.
[5] Netea MG, Van der Graaf C, Van der Meer JW, et al. Recognition of fungal pathogens by Toll-like receptors[J]. Eur J Clin Microbiol Infect Dis, 2004, 23(9): 672-676.
[6] Netea MG, Warris A, Van der Meer JW, et al. Aspergillus fumigatus evades immune recognition during germination through loss of TLR4-mediated signal transduction[J]. J Infect Dis, 2003, 188(2):320-326.
[7] Bellocchio S, Montagnoli C, Bozza S, et al. The contribution of Toll-like/IL-1 receptor superfamily to innate and adaptive immunity to fungal pathogens in vivo[J]. J Immunol, 2004, 172(5):3059-3069.
[8] Park SJ, Mehrad B. Innate immunity to Aspergillus species[J]. Clinical microbiology reviews, 2009, 22(4): 535-551.
[9] Bozza S, Zelante T, Moretti S, et al. Lack of Toll IL-1R8 exacerbates Th17 cell responses in fungal infection[J]. J Immunol, 2008, 180(6):4022-4031.
[10] Moretti S, Bellocchio S, Bonifazi P, et al. The contribution of PARs to inflammation and immunity to fungi[J]. Mucosal Immunol, 2008, 1(2):156-168.
[11] Gersuk GM, Underhill DM, Zhu L, et al. Dectin-1 and TLRs permit macrophages to distinguish between different Aspergillus fumigatus cellular states[J]. J Immunol, 2006, 176(6):3717-3724.
[12] Serrano-Gómez D, Domínguez-Soto A, Ancochea J, et al. Dendritic cell-Specific intercellular adhesion molecule 3-grabbing nonintegrin mediates binding and internalization of Aspergillus fumigatus conidia by dendritic cells and macrophages[J]. J Immunol, 2004, 173(9):5635-5643.
[13] den Dunnen J, Gringhuis SI, Geijtenbeek TB. Innate signaling by the C-type lectin DC-SIGN dictates immune responses[J]. Cancer Immunol Immunother, 2009, 58(7):1149-1157.
[14] Sainz J, Lupiáñez CB, Segura-Catena J, et al. Dectin-1 and DC-SIGN polymorphisms associated with invasive pulmonary aspergillosis infection[J]. PLoS One, 2012, 7(2):e32273.
[15] Madan T, Kaur S, Saxena S, et al. Role of collectins in innate immunity against aspergillosis[J]. Med Mycol, 2005,43(Suppl1):S155-163.
[16] Brummer E, Stevens DA. Collectins and fungal pathogens: roles of surfactant proteins and mannose binding lectin in host resistance[J]. Med Mycol, 2010, 48(1):16-28.
[17] Salvatori G, Campo S. Current understanding of PTX3 protective activity on Aspergillus fumigatus infection[J]. Med Mycol, 2012, 50(3):225-233.
[18] Kunes P, Holubcova Z, Kolackova M, et al. Pentraxin 3(PTX3): an endogenousmodulator of the inflammatory response[J]. Mediators Inflamm, 2012, 2012(920517):1-10.
[19] Mansour MK, Levitz SM. Interactions of fungi with phagocytes[J]. Curr Opin Microbiol, 2002, 5(4): 359-365.
[20] Schaffner A, Douglas H, Braude AI, et al. Killing of Aspergillus spores depends on the anatomical source of the macrophage[J]. Infect Immun, 1983, 42(3):1109-1115.
[21] Fallon JP, Reeves EP, Kavanagh K. Inhibition of neutrophil function following exposure to the Aspergillus fumigatus toxin fumagillin[J]. J Med Microbiol, 2010, 59(66):625-633.
[22] Boyle KB, Stephens LR, Hawkins PT. Activation of the neutrophil NADPH oxidase by Aspergillus fumigatus[J]. Ann N Y Acad Sci, 2012, 1273:68-73.
[23] Aratani Y. Role of myeloperoxidase in the host defense against fungal infection[J]. Nihon Ishinkin Gakkai Zasshi, 2006, 47(3):195-199.
[24] Park SJ, Mehrad B. Innate immunity to Aspergillus species[J]. Clinical microbiology reviews, 2009, 22(4): 535-551.
[25] Morrison BE, Park SJ, Mooney JM, et al. Chemokine-mediated recruitment of NK cells is a critical host defense mechanism in invasive aspergillosis[J]. J Clin Investig, 2003, 112(12):1862-1870.
[26] Saluja R, Metz M, Maurer M. Role and relevence of mast cells in fungal infections[J]. Frontiers in Immunology, 2012, 3(146):1-11.
[27] Urb M, Pouliot P, Gravelat F, et al. Aspergillus fumigatus induces immunoglobulin E-independent mast cell degranulation[J]. J Infect Dis, 2009, 200(3): 464-472.
[28] Bozza S, Gaziano R, Spreca A, et al. Dendritic cells transport conidia and hyphae of Aspergillus fumigatus from the airways to the draining lymph nodes and initiate disparate Th responses to the fungus[J]. J Immunol, 2002, 168(3):1362-1371.
[29] Ramirez-Ortiz ZG, Means TK. The role of dendritic cells in the innate recognition of pathogenic fungi (A.fumigatus,C.neoformans and C.albicans)[J].Virulence, 2012, 3(7):635-646.
[30] Romani L. Immunity to fungal infections[J]. Nat Rev Immunol, 2011, 11(4):275-288.
[31] Botterel F, Gross K, Ibrahim-Granet O. Phagocytosis of Aspergillus fumigatus conidia by primary nasal epithelial cells in vitro[J]. BMC Microbiol, 2008, 8(97):1-9.
[32] Osherov N. Interaction of the pathogenic mold Aspergillus fumigatus with lung epithelial cells[J]. Front Microbiol, 2012, 3(346):1-9.
[33] 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]. J Biol Chem, 2008, 283(45):30513-30521.
[34] Kamai Y, Chiang LY, Lopes Bezerra LM, et al. Interactions of Aspergillus fumigatus with vascular endothelial cells[J]. Med Mycol, 2006, 44 (Suppl 1):S115-117.
[35] 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[J].Infect Immun, 2008, 76(8):3429-3438.
[36] 孙铮,赵作涛,万喆,等.烟曲霉感染的宿主防御机制以及相关免疫学研究进展[J].中国真菌学杂志, 2010, 5(5):307-311.
[37] Zelante T, Bozza S, De Luca A, et al. Th17 cells in the setting of Aspergillus infection and pathology[J]. Medical Mycology, 2009, 47 (Suppl 1):162-169.
[38] McCormick A, Loeffler J, Ebe F. Aspergillus fumigatus: contours of an opportunistic human pathogen[J]. Cellular Microbiology, 2010, 12(11):1535-1543.