马尔尼菲青霉菌野生株和临床分离株致病力动物实验研究
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摘要
目的对不同来源的马尔尼菲青霉菌(Penicillium marneffei,PM)菌株的致病过程和致病力情况进行初步探讨。
     方法分别将来源于广西银星竹鼠的PM菌株(野生菌株)及广西地区PSM患者的血液培养分离的PM菌株(临床分离菌株)的菌悬液经腹腔注射感染健康小鼠,然后按时间分批处死,肉眼观察并分析脏器感染情况;取其内脏(肝、脾、肺、心、肾、肠、脑、肌肉、胸骨、皮肤)及颈动脉血行真菌培养并比较阳性率差异;分析死亡小鼠的一般状况;主要脏器行组织病理切片观察了解其病理改变。
     结果发现小鼠感染的发病率为100%;不同时期小鼠内脏病变程度有差异,且内脏病变程度随着时间推移而逐渐减轻;A、B两组小鼠部分脏器真菌培养阳性率有明显差异;A、B两组小鼠的死亡率无显著性差异,死亡小鼠存活时间的中位数为24.42天;A、B两组小鼠肝、脾、肺、肠、肾等脏器的基本病理形态有改变,C组脏器无病理改变。
     结论不同来源的PM菌株经腹腔注射感染途径均可使小鼠致病;说明竹鼠体内野生PM与人类马尔尼菲青霉病(Penicilliosis marneffei,PSM)关系密切;具有正常免疫功能的小鼠感染PM后可以逐渐恢复;本实验可以作为研究马尔尼菲青霉病的发病机制、病理学及致病力等的一个手段。
Objective To study the pathopoiesis and process of wild isolates and clinical isolates penicillium mameffei on mice through abdominal cavity injection.
     Methods The conidia suspension of wild isolates and clinical isolates penicillium mameffei was inoculated into the abdominal cavity of healthy mice respectively.We killed the mice in batch on time,to observe the infection status of internal organs and masculine rate of PM infections,to analyze general state for death mice,and to study histopathological microscopical diversity for main internal organs.
     Result The incidence of mice infected with penicillium marneffei was 100%;The affection of splanchna was diverse in five periods,and it was less and less prominent with time-lapse.The masculine rate of PM infections was different for some different organs between group A and group B.The mortality rate was identical between group A and group B,and the median of survival time was 24.42 days for death mice;The histopathological microscopical diversity was evident for main internal organs between group A and group B, and there was no change in group C.
     Conclusion Penicillium mameffei of different source is pathogenic on mice through abdominal cavity injection;It indicates that the relationship of wild isolates PM and Penicilliosis mameffei in people is intimate;Infection could recover spontaneously by degrees in immunocompetent mice;This experimental study might be suitable to study pathogenesis,pathology and virulence of penicilliosis marneffei.
引文
1 Singh PN,Ranjana K,Singh YI,et al.Indigenous Disseminated Penicillium marneffei Infection in the State of Manipur,India:Report of Four Autochthonous cases.Clin Microbiol,1999,37:2699-2702.
    2 Supparatpinyo K,Khamwan C,Baosoung V,et al.Disseminated Penicillium marneffei Infection in Southeast Asia.Lancet.1994,344:110-113.
    3 T.J.Walsh,A.H.Groll.Emerging fungal pathogens:evolving challenges to immunocompromised patients for the twenty first century.Transplant Infectious Disease.1999,1:247-261.
    4 Valeyrie L,Botterel F,Minozzi C,et al.Prolonged fever revealing disseminated infection due to Penicillium marneffei in a French HIV-seropositive patient.AIDS.1999,13:731.
    5 Filiotou Anna,Velegraki Aristea,Giannaris Markos,et al.First Case of Penicillium marneffei Fungemia in Greece and Strain Susceptibility to Five Licensed Systemic Antifungal Agents and Posaconazole.American Journal of the Medical Sciences.2006,332:43-45.
    6 吴易,李菊裳,梁伶.广西银星竹鼠与人马尔尼菲青霉病关系的研究.中国皮肤性病学杂志.2004,18:196-198
    7 Nongnuch Vanittanakom,Chester R.,Cooper Jr.,et al.Penicillium marneffei Infection and Recent Advances in the Epidemiology and Molecular Biology Aspects.Clinical Microbiology Reviews,2006,19:95-110.
    8 梁伶,李菊裳.马尔尼菲青霉的生态学研究.广西医科大学学报.1999,16:602-604.
    9 马韵,邓卓霖,李山,等.马尔尼菲青霉不同菌株的免疫原性和致病力研究.广西医科大学学报.1994,11:128-130.
    10 Capponi MP,Segretain G,Sureau G.Penieilliosis de Rhizomys sinensis[J]. Bull Soc Pathol Exot Filiales.1956,49:418-421.
    11 DiSalvo AF,Fickling AM,AjelloL.Infection caused by penicillium marneffei:description of first natural infection in man.Am J Clin Pathol,1973,60:259-263
    12 Harish Gugnani,Matthew C.Fisher,Anubha Paliwal-Johsi,et al.Role of Cannomys badius as a Natural Animal Host of Penicillium marneffei in India.Journal of Clinical Microbiology.2004,11:5070-5075
    13 李菊裳,潘乐泉,吴绍熙.马尔尼菲青霉病.中国人兽共患病杂志.1990,2:54-56
    14 李山,邓卓霖,马韵.广西鼠类携带马尔尼菲青霉的研究.广西医学,1995,17(1):1-2.
    15 Kudeken N,Kawakami K,Kusano N,et al.Cell-mediated immunity in host resistance against infection caused by Penicillium marneffei.Journal of Medical & Veterinary Mycology.1996,34:371-378.
    16 Cui J,Tanaka R.,Taguchi H,et al.Histopathological and electron microscopical studies on experimental Penicillium marneffei infection in mice.Journal of Medical & Veterinary Mycology.1997,35:347-353.
    17 Kudeken N,Kawakami K,Saito A.CD4~+ T cell mediated fatal hyperinflammatory reactions in mice infected with Penicillium marneffei.Clin Exp Immunol.1997,107:468-473.
    18 刘栋华,谭升顺,梁伶,等.经皮肤损伤感染马尔尼菲青霉菌致病力动物实验研究.中国皮肤性病学杂志.2006,20:324-326.
    19 Woods JP.Knocking on the right door and making a comfort-able home:Histoplasma capsulatum intracellular pathogenesis.Curr Opin Microbiol,2003,6(4):327-331.
    20 邓卓霖,马韵.酷似组织胞浆菌病的马尔尼菲青霉病.中华病理学杂志,1999,28(5):348-349.
    21 马韵,邓卓霖,罗虹.马尔尼菲青霉病不同类型病变中免疫反应观察.广西医科大学学报 1994,11(4):361-364
    22 朱宏,崔进,刘明,等.竹鼠马尔尼菲青霉菌感染的病理学研究.哈尔滨医科大学学报.2000,34(6):404-405
    23 Hamilton AJ,Jeavons L,YoungchimS,et al.Recognition of fibronectin by Penicillium marneffei conidia via sialic acid dependent process and its relationship to the interaction between conidia and laminin.Infect Immun 1999,67:5200-5205.
    24 Amnat Yousukh,Prapan Jutavijittum,Pises Pisetpongsa,et al.Clinicopathologic Study of Hepatic Penicillium marneffei in Northern Thailand.Archives of Pathology & Laboratory Medicine;2004,128:191-194
    25 P.Khongkunthian,W.Isaratanan,L.P.Samaranayake,et al.Oro-facial manifestations of Penicillium marneffei infection in a Thai patient with AIDS.Mycoses.2002,45:411-414
    26 Alex Andrianopoulos.Control of morphogenesis in the human fungal pathoen Penicillium marneffei.Int.J.Med.Microbiol.292:331-334
    27 Kawakmai K,Tohyama M,Xie Q,et al.IL-12 protects Mice against pulmonary and disseminated infection caused by Cryptococcus neoformans.Clin Exp Immunol,1996,10(2):208-214.
    28 Romani L,Mencacci A,Cenci E,et al.Neutrophil production of IL-12 and IL-10 in candidiasis and efficancy of IL-12 therapy in neutropenic mice.J Immunol,1997,158(11):5349-5356.
    29 Keya S,Salamatu SM,Latz E,etal.The Antifungal Drug Amphotericin B Promotes Inflammatory Cytokine Release by a Toll-like Receptor and CD14-dependent Mechanism. The Journal of Biological Chemistry, 2003,278(39):37561-37568.
    30 Miller RF, Semple SJ. Glucocorticoid therapy for severe Pneumocystis carinii pneumonia. J Infect 1990,21: 131-137
    31 Bozza S, Perruccio K, Montagnoll C, et al. A dendritic cell vaccine against invasive aspergillosis in allogeneic hematopoietic transplantation. Blood, 2003,102:3807-3814
    32 Ahuja SS, Mummidi S, Malech HL,et al. Human dendritic cell (DC)-based anti-infective therapy: engineering DCs to secrete functional IFN- γ and IL-12. J Immunol,1998,16(2):868-876.
    33 Po-Ren Hsueh, Lee-Jene Teng, Chien-Ching Hung,et al. Molecular evidence for strain dissemination of Penicillium marneffei: An emerging pathogen in Taiwan. The Journal of Infectious Diseases. 2000,181: 1706-1712.
    1 Capponi MP,Segretain G,Sureau G.Penieilliosis de Rhizomys sinensis.Bull Soc Pathol Exot Filiales.1956,49:418-421.
    2 Segretain G.Penicillium marneffei n.sp.,agent d'une mycose du systeme reticuloendothelial.Mycopathol Mycol Appl 1959,11:327-353.
    3 Di Salvo DA,Fickling AM,Ajello L.Infection caused by Penicillium marneffei.Description of first natural infection in man.Am J Clin Pathol 1973;60:259-263.
    4 Pautler KB,Padhye AA,Ajello L.Imported penicilliosis marneffei in the United States:report of a second human infection.Sabouradia.J Med Vet Mycol 1984,22:433-438.
    5邓卓霖.进行性播散性马尔尼菲青霉病.广西医学院学报,1984,1:1-3
    6 Drouhet E.Penicilliosis due to Penicillium marneffei:a new emerging systemic mycosis in AIDS patients travelling or living in southeast Asia.J Mycol Med 1993,4:195-224.
    7 Deng ZL,Connor DH.Progressive disseminated penicilliosis caused by Penicillium marneffei:report of eight cases and differentiation of the causative organism from Histoplasma capsulatum.Am J Clin Pathol 1985,84:323-327.
    8 Jayanetra P,Nitiyanant P,Ajello L.Penicillium marneffei in Thailand:report of five human cases.Am J Trop Med Hyg 1984,33:637-644.
    9 Deng ZL,Ribas JL,Gibson DW,et al.Infections caused by Penicillium marneffei in China and Southeast Asia.Review of eighteen cases and report of four more Chinese cases.Rev Infect Dis 1988,10:640-652.
    10 Chan YF,Chow TC.Ultrastructural observations on Penicillium marneffei in natural human infection.Ultrastruct Pathol 1990,14:439-452.
    11 So S,Chau P,Jones BM.A case of invasive penicilliosis in Hong Kong with Immunolo gic evaluation.Am J Respir Dis 1985,131:662-665.
    12 Piehl MR,Kaplan RL,Haber MH.Disseminated penicilliosis in a patient with acquired immunodeficiency syndrome.Arch Pathol Lab Med 1988,112:1262-1264.
    13 Supparatpinyo K,Khamwan C,Baosoung V,et al.Disseminated Penicillium marneffei infection in southeast Asia.Lancet 1994,344:110-113.
    14 T.J.Walsh,A.H.Groll.Emerging fungal pathogens:evolving challenges to immunocompromised patients for the twenty first century.Transplant Infectious Disease.1999,1:247-261.
    15 莫让辉,唐小平,蔡卫平等.艾滋病合并播散性马尔尼菲青霉菌病41例临床分析.中国实用内科杂志.2006,24:1953-1955
    16 Deng ZL,Yun M,Ajello L.Human penicilliosis marneffei and its relation to the bamboo rat(R.pruinosus).J Med Vet Mycol 1986,24:383-389.
    17 Ajello L,Padhye AA,Sookroongreung S,et al.Occurrence of Penicillium marneffei infections among wild bamboo rats in Thailand.Mycopathologia 1995,131:1-8.
    18 Chariyalertsak S,Vanittanakom P,Nelson KE,et al.Rhizomys sumatrensis and Cannomys badius,new natural animal hosts ofPenicillium marneffei.J Med Vet Mycol.1996,34:105-110.
    19 Rataporn Ungpakorn.Cutaneous manifestations of Penicillium marneffei infection.Current Opinion in Infectious Diseases.2000,13:129-134.
    20 Chariyalertsak S,Sirisanthana T,Supparatpinyo K,et al.Case-control study of risk factors for Penicillium marneffei infections in human immunodeficiency virus -infected patients in northern Thailand.Clin Infect Dis.1997,24:1080-1086.
    21 Chariyalertsak S,Sirisanthana T,Supparatpinyo K,et al.Season variation of disseminated Penicillium marneffei infections in northern Thailand:A clue to reservoir? J Infect Dis.1996,173:1490-1493.
    22 Hamilton AJ,Jeavons L,YoungchimS,et al.Recognition of fibronectin by Penicillium marneffei conidia via sialic acid dependent process and its relationship to the interaction between conidia and laminin.Infect Immun.1999,67:5200-5205.
    23 Rongrungruang Y,Levitz SM.Interactions of Penicillium marneffei with human leukocytes in vitro.Infect Immun.1999,67:4732-4736.
    24 Sirisanthana V,Sirisanthana T.Disseminated Penicillium marneffei infection in human immunodeficiency virus-infected children.Pediatr Infect Dis J.1995,14:935-940.
    25 Jones PD,See J.Penicillium marneffei infection in patients infected with human immunodeficiency virus:late presentation in an area of nonendemicity[Letter].Clin Infect Dis.1992,15:744.
    26 刘艳,詹能勇,李慧涓等.艾滋病合并播散性马尔尼菲青霉菌感染临床及治疗转归研究,中华传染病杂志.2005,23(4):256-259
    27 Sirisanthana T,Supparatpinyo K.Epidemiology and management of penicilliosisin human immunodeficiency virus-infected patients(Review).Int J Infect Dis.1998;3:48-53.
    28 Yuen KY,Wong SSY,Tsang DNC,et al.Serodiagnosis of Penicillium marneffei infection.Lancet.1994,344(8920):444-445.
    29 Cao L,Chan CM,Lee C,et al.MP1 encodes an abundant and highly antigenic cell wall mannoprotein in the pathogenic fungus Penicillium marneffei.Infect Immun.1998,66(3):966-973.
    30 Wong SSY,Wong KH,Hui WT,et al.Differences in clinical and laboratory diagnostic characteristics of penicilliosis marneffei in human immunodeficiency virus(HIV)- and non-HIV-infected patients.J Clin Microbiol.2001,39(12):4535-4540.
    31 Cao L,Chen D-L,Lee C,et al.Detection of specific antibodies to an antigenic mannoprotein for diagnosis of Penicillium marneffei penicilliosis.J Clin Microbiol.1998.36:3028-3031.
    32 Desakorn V,Smith MD,Walsh AL,et al.Diagnosis of Penicillium marneffei infection by quantitation of urinary antigen by using an enzyme immunoassay.J Clin Microbiol.1999.37:117-121
    33 Nittayananta W.Penicilliosis marneffei:another AIDS defining illness in Southeast Asia.Oral Dis.1999,5(4):286-293.
    34 曹存巍,邓卓霖,罗虹等.原位杂交技术鉴定马尔尼菲青霉.中国皮肤性病学杂志.2004,18(8):462-463
    35 Supparatpinyo K,Nelson KE,Merz WG,et al.Response to antifungal therapy by human immunodeficiency virusinfected patients with disseminated Penicillium marneffei infections and in vitro susceptibilities of isolates from clinical specimens.Antimicrob Agents Chemother,1993,37:2407-2411.
    36 Sirisanthana T,Supparatpinyo K,Perriens J,et al.Amphotericin B and itraconazole for treatment of disseminated Penicillium marneffei infection in human immunodeficiency virus-infected patients.Clin Infect Dis,1998,26:1107-1110.
    37 Supparatpinyo K,Perriens J,Nelson KE,et al.A controlled trial of itraconazole to prevent relapse of Penicillium marneffei infection in patients infected with the human immunodeficiency virus.N Engl J Med.1998,339:1739-1743.
    38 Kawakmai K,Tohyama M,Xie Q,et al.IL-12 protects Mice against pulmonary and disseminated infection caused by Cryptococcus neoformans.Clin Exp Immunol.1996,10(2):208-214.
    39 Romani L,Mencacci A,Cenci E,et al.Neutrophil production of IL-12 and IL-10 in candidiasis and efficancy of IL-12 therapy in neutropenic mice.J Immunol. 1997,158(11):5349-5356.
    40 Keya S, Salamatu SM, Latz E, etal. The Antifungal Drug Amphotericin B Promotes Inflammatory Cytokine Release by a Toll-like Receptor and CD14-dependent Mechanism. The Journal of Biological Chemistry. 2003, 278(39):37561-37568.
    41 Kudeken N, Kawakami K, Saito A. CD4~+ T cell mediated fatal hyperinflammatory reactions in mice infected with Penicillium marneffei. Clin Exp Immunol. 1997,107: 468 - 473.
    42 Miller RF, Semple SJ. Glucocorticoid therapy for severe Pneumocystis carinii pneumonia. J Infect. 1990,21:131-137
    43 Bozza S, Perruccio K, Montagnoll C, et al. A dendritic cell vaccine against invasive aspergillosis in allogeneic hematopoietic transplantation. Blood. 2003,102:3807-3814
    44 Ahuja SS, Mummidi S, Malech HL,etal. Human dendritic cell (DC)-based anti-infective therapy: engineering DCs to secrete functional IFN-γ and IL-12. J Immunol.1998,16(2): 868-876.

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