Cryptococcus neoformans, a facultative intracellular pathogen of macrophages, is unique among medically important fungi in its possession of a polysaccharide capsule. Capsule represents the organism's major virulence factor. In the absence of opsonins, binding of encapsulated C. neoformans to macrophages is minimal. Following incubation in serum, C. neoformans potently activates complement, resulting in surface deposition of the third component of complement. Macrophages bind and phagocytose opsonized C. neoformans via three major complement receptors (CR) for C3 fragments, designated CD35 (CR1), CD 11 b/CD 18 (CR3), and CD 11 cICD 18 (CR4). Antibody in normal human serum generally lacks opsonic activity, although vaccination can elicit anticapsular antibodies that are opsonic. The major component of cryptococcal capsule, glucuronoxylomannan (GXM), is shed from the fungus and circu-lates in the blood and cerebrospinal fluid of patients with cryptococcosis. Cellular receptors defined or GXM include CD 14, toll-like receptor-2, toll-like receptor-4, and CD 18. GXM binding to macro-phage receptors triggers activation of nuclear factor- _KB, but not mitogen-activated protein kinases. This results in no proinflammatory gene expression or release. C. neoformans also secretes mannoproteins, which are recognized by mannose receptors as well as by mannose-binding lectin, perhaps in conjunction with CD 14. Strategies directed at modulating how intact C. neoformans and its released components are recognized by phagocytes could lead to novel approaches to treating cryptococcosis

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クリプトコッカスはエイズや血液悪性疾患を代表とする免疫低下宿主に合併する日和見真菌感染症である.感染防御の主体は細胞性免疫であり, Th1サイトカイン及びIL-12, IL-18が重要な役割を担う.近年, NK, NKT, γδT細胞などから構成される自然免疫の機能的意義が明らかにされるにつれ大きな注目を集めつつある.特に, NKT細胞は糖脂質抗原の認識に関与することが明らかにされており, 腫瘍免疫や自己免疫疾患との関連で多くの知見が蓄積されている.本稿では, 感染とNKT細胞に関するこれまでの報告について概説するとともに, クリプトコッカス感染に対する初期防御と獲得免疫の成立過程におけるNKT細胞の役割について自験データを紹介しながらまとめてみた.

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This understood without starting paper describes general histopathological features of deep seated mycoses in patients with acquired immunodeficiency syndrome (AIDS) detailed histological examination on cryptococcal lesions with a consideration of morphological modification caused by treatment with highly active antiretroviral therapy (HAART).
In a histopathological review of 164 patients with total human immunodeficiency virus (HIV) infection, the microscopical appearance of esophageal candidiasis which was common in those with single organ involvement revealed necrotic debris containing proliferating hyphae at the site of mucosal erosions without fungal invasion of underlying tissue. The incidence of oral and esophageal candidiasis was followed by that of pulmonary aspergillosis and Candida pneumonia. Nineteen patients including one treated with HAART had generalized cryptococcosis, representing the most common generalized fungal disease. The essential histologic features of the disease were yeast cell proliferation with a histiocytic response, but only minor lymphocytic and neutrophilic components. This was different from those induced by both Candida and Aspergillus infections. Three histologic patterns were recognized in the pulmonary cryptococcal lesions, two of which could be graded with respect to the degree and type of inflammatory reaction. The first was a mild one consisting of small scattered foci of intra-alveolar cryptococcal proliferation with a histiocytic response. The second pattern involved massive cryptococcal infection, which might have been simply more extensive than that in the former. Capillary involvement of alveolar septa was an important common finding in the eighteen patients who had not been treated with HAART. The absence of T cells and decreasing function of antigen presenting activity in histiocytes were confirmed by immunohistological examination. These findings suggest that the lungs of AIDS patients without HAART offer little resistance to bloodstream diss mination by Cryptococci. The third pattern demonstrated in the patient treated with HAART was characterized by the presence of CD4 + cells, greater response of histiocytes and multinucleated giant cell formation, and lack of massive capillary involvement.

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真菌感染は, 好中球機能低下による日和見感染と深くかかわっていることが明らかになってきている.好中球のもつlysosome酵素のmyeloperoxidase (MPO) と活性酸素産生酵素NADPH oxidaseの欠損した患者の好中球機能の解析や, これら遺伝子のノックアウトマウスを用いたin vivoの感染実験の解析から, ラジカル酸素産生能の低下が真菌感染抵抗性の低下をもたらしていることが解明された.MPO酵素欠損患者ではCandida albicansの感染抵抗が低下していることが欧米で報告されている.さらに, われわれが作製したMPO遺伝子ノックアウトマウスによるinvivoの感染実験からも一義的にC. albicansへの感染抵抗が低下していることが判明している.一方, NADPH oxidase欠損は, 慢性肉芽腫症 (CGD) となって重篤化する疾患で, Aspergillus感染への抵抗性が極度に低下していることが特徴である.NADPH oxidaseは, 膜蛋白質cytochrome b558と細胞質蛋白質p47phox, p67phox, p40phox等の分子群からなり, 好中球の活性化によって, これら分子が膜に集合してユニットとなって活性を発現する.また, 真菌の慢性的な感染は, 血管炎やアレルギーの誘発にもつながっている。

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Aspergillosis has become the biggest cause of death among mycoses in Japan. The main causative agent is Aspergillus fumigatus and its virulence factors have been variously investigated, yet much remains to be clarified.
We recently found that the culture filtrate of A. fumigatus has potent anti-leukocyte activity. It seriously damages macrophages and hampers the function of polymorphonuclear neutrophils. The filtrate is also active in vivo : when injected intraperitoneally, the culture filtrate lowered the survival of mice infected with A. fumigatus. This activity becomes overt within 24 hours of culture of the fungus. Although the mechanism of pathogenicity of A. fumigatus is believed to be somewhat complex, we suggest the activities shown in the culture filtrate may play a crucial role in the development of the infection.

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Thirty-one single ascospore cultures were obtained from one ascoma produced in mating of RV 26678 (+) (Institut de Medicine Tropicale, Antwerp, Belgium) and KMU 4169 (-) (Dept. Dermatology, Kanazawa Medical University, Uchinada, Japan), which are genetically different strains of Arthroderma benhamiae. The isolation was performed with the aid of an inverted microscope and a binocular microscope. The internal transcribed spacer (ITS) regions of the nuclear ribosomal RNA gene of all the ascospore cultures were analyzed by restriction fragment length polymorphism (RFLP) with the restriction enzyme Hinfl. The mating types of all the single-ascospore cultures were also checked. Eight cultures had mating type (+) and RV 26678 genotype, 10 had mating type (-) and RV 26678 genotype, 6 had mating type (+) and KMU 4169 genotype and 7 had mating type (-) and KMU 4169 genotype. There was no linkage between the mating types and the genotypes, implying that the genes control the mating behavior and the genes of ribosomal RNA are on different chromosomes from each other. The hybrids comprised half of the isolates and so they were actually from the ascospores and not from the microconidia or the peridial hyphae.

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Hortaea werneckii, a black yeast and the causative agent of tinea nigra (a superficial type of dermatomycosis), is a human pathogen and is also found in the environment. It is not highly pathogenic but in the last fifteen to twenty years has been isolated from various human and environmental sources in Japan. As far as we know, there has been no report on the isolation of H. werneckii from animals. Recently, we found a case of a guinea pig with dark superficial lesions on the palm and dorsal areas. Cultural and morphological studies of scrapings from the lesion showed that the causative agent was a black yeast, which was identified as H. werneckii by morphological study and molecular biological screening. Dl/D2 region of the 26S large subunit rDNA gene of this isolate was identical to those of 11 other H. werneckii isolates used as reference strains in this study. This is the first case recorded of tinea nigra caused by H, werneckii in a guinea pig.

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Trichophyton rubrumに対するチオカルバミン酸系抗真菌剤liranaftateの殺菌活性を主として, ミリフレックス®-100テストシステムを用いてのMICおよびMCCを求める方法とtime-killcurve法により6種抗真菌剤との比較を行った.T.rubrum分生子に対するMICおよびMCCを経日的に測定した結果, liranaftateおよびlanoconazoleの作用14日目のMIC値はいずれも0.009μg/mlであり, 最も優れていた.LiranaftateのMCC値は作用9日目以降小さくなりはじめ, 作用14日目のMCC値は0.039μg/mlであった.TolciclateのMCC値も作用9日目以降小さくなったが, amorolfine, lanoconazole, neticonazole, clotrimazoleおよびbifonazoleのMCC値は作用14日目まで全く低下しなかった.この結果は発芽分生子に対しても大きな差が認められなかった.
Time-killcurveの検討では, liranaftateおよびtolciclateは2～32×MICで作用7～9日目に生菌数が測定限界以下となった.Amorolfineは作用菌濃度が低い場合, 作用14日目に測定限界以下となったが, 4種アゾール剤はいずれも作用14日目までにほとんど測定限界以下に低下しなかった.
以上の結果より, 殺菌活性の強さは系統別にチオカルバミン酸系, モルホリン系, アゾール系の順であることが示唆された.

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We report a case of seborrheic blepharitis treated with oral itraconazole during a short period. Direct examination using Parker KOH revealed numerous hyphae and spores of Malassezia in the scale. Low-dose itraconazole pulse therapy (200 mg daily, 7 days a month) was quite effective. This is the second case in which we also observed a unique fungal conformation which looked like tinea versicolor. The evidence strongly suggests that Malassezia is one of the major causative agents of Seborrheic Blepharitis.

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