condition (54/219, 24.6%). • Among HIV-negative patients, liver diseases (HBV
carrier or cirrhosis) were common (30.2%)
Taiwan Infectious Diseases Study Network for Cryptococcosis. PLoS One. 2013 Apr 17;8(4):e61921.
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pathogenesis
The capsule is the most important virulence factor of the fungal pathogen Cryptococcus neoformans. • The structure • Production Of the capsule • adhesion of Cryptococcus neoformans to epithelial lung cells • protective immune responses against cryptococcosis
• GXM against alveolar macrophages (AM) .
Mechanisms of immune evasion in fungal pathogens.
1 Microbiology. 2001 Aug;147(Pt 8):2355-65. 2 Curr Opin Microbiol. 2011 Dec;14(6):668-75.
PS，etc alveolar microenvironment
capsule?
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adhesion to epithelial lung cells
• an adhesion-like interaction between MP on the fungal surface and the complementary receptor molecules on the epithelial cells.
Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases .J Infect Chemother. 2014 Oct 29
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Epidemiology IV
• 219 patients with proven cryptococcosis at 20 hospitals in Taiwan, 1997-2010
A multicentre retrospective study of pulmonary mycosis clinically proven from 1998 to 2007
Totally 474 cases of pulmonary mycosis from 16 centers in10 cities.
Regulation of cryptococcal capsular polysaccharide by iron. J Infect Dis. 1993 Jan;167(1):186-90.
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Production Of the capsule III
• capsule enlargement in living C. neoformans cells was influenced by Ca(2+) in the culture medium.
➢ 210 isolates were C. neoformans (95.9%); ➢ 9 isolates were C. gattii (4.1%). • 15.4% did not have any underlying condition. • HIV infection was the most common underlying
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Epidemiology V
• Clinical analysis of 76 patients pathologically diagnosed with pulmonary cryptococcosis.
• Of 76 patients (54 males and 22 females), 41 (53.95%) were immunocompetent and 35 out of the 41 were asymptomatic.
Eukaryot Cell. 2007 Aug;6(8):1400-10.
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Production Of the capsule IV
• based on the axial lengthening of PS molecules.
Capsule of Cryptococcus neoformans grows by enlargement of polysaccharide molecules.Proc Natl Acad Sci U S A. 2009 Jan 27;106(4):1228-33.
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关于隐球菌Ｃｒｙｐｔｏｃｏｃｃｕｓ
• 带厚荚膜的酵母菌（乳胶凝集试验） • 腐生菌：土壤、鸽粪、霉烂蔬菜、水果等 • 感染部位：中枢神经系统、皮肤、肺 • 感染途径：吸入呼吸道经血行播散到其它部位 • 分型：17个种、18个变种 （新生隐球菌及变种具有致病性）
---roduction Of the capsule I
• CA/CO2-sensing pathways .
1 Regulation of capsule synthesis by carbon dioxide． J Clin Invest， 1985， 76( 2) : 508-516． 2 Comparative transcriptome analysis of the CO2 sensing pathway via differential expression of carbonic anhydrase in Cryptococcus neoformans.Genetics. 2010 Aug;185(4):1207-19.
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immune response
• SP-D increases susceptibility to C. neoformans infection by promoting C. neoformans-driven pulmonary IL-5 and eosinophil infiltration.
既往：体健。否认性病冶游史。家中曾养宠物（鸽子、狗）。 查体：T：37.9 ℃，浅表淋巴结不大，右下肺可及湿啰音。
辅助检查：
血常规、肝肾功能、D-二聚体正常；ESR：65mm/h，CRP： 48mg/L；血气分析正常；HIV（-） PPD试验阴性；LA试验、G试验阴性（送至C院检测）
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2010.9.6 A院CT 2010.9.27 A院CT
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病史介绍
A院气管镜检查： 镜下：未见明显异常； 右下肺灌洗和刷检：未见恶性细胞、TB阴性。
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2010.10.12 B院 CT引导下经皮肺穿刺
• 病理结果确诊： 肺隐球菌病
➢上皮样肉芽肿性病变； ➢成堆隐球菌
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几点疑问
• 真菌病一般都是免疫功能低下的患者 • 隐球菌如何侵袭到肺的 • LA试验阴性 • 肺隐球菌病CT表现和肺炎一样
Front Cell Infect Microbiol. 2014 Aug 19;4:106.
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Phagocytosis defence
• Size of Cryptococcus neoformans.
Dynamic changes in the morphology of Cryptococcus neoformans during murine pulmonary infection.
• pulmonary aspergillosis(1 80 cases，37．9％) • pulmonary candidiasis(162 cases，34．2％) • pulmonary cryptococcosis(74 cases，15．6％) • pneumocystis cafinii pneumonia(23 cases，4.8％) • pulmonary mucormycosis(10 cases，2．1％)
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The structure of capsule
This structure consists of highly hydrated polysaccharides, including • glucuronoxylomannan (GXM)，葡萄糖醛 酸木糖甘露聚糖 • galactoxylomannan (GalXM) ，半乳糖木糖 甘露聚糖 • mannoproteins (MPs)，甘露糖蛋白，less than 1% of the capsular weight
Shanghai Pulmonary Hospital .Eur Respir J. 2012 Nov;40(5):1191-200.
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summary
• approximately half of patients had no underlying diseases
• a significant number of patients were asymptomatic
中华结核和呼吸杂志，2011,34(2)
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Epidemiology II
Meta-Analysis of Clinical Manifestations of Pulmonary Cryptococcosis in China Mainland • 69.7 % patients had no underlying diseases． • The common underlying diseases were ➢acquired immune deficiency syndrome( AIDS) ➢diabetes ➢malignant tumor