Role of extracellular phospholipases and mononuclear phagocytes in dissemination of cryptococcosis in a murine model
Role of extracellular phospholipases and mononuclear phagocytes in dissemination of cryptococcosis in a murine model
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DOI：
10.1128/iai.72.4.2229-2239.2004
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发表时间：
2004-04-01
影响因子：
3.1
通讯作者：
Wright, L
中科院分区：
文献类型：
--
作者：
Santangelo, R;Zoellner, H;Wright, L
分泌型磷脂酶B(PLB)活性促进新生隐球菌在体外巨噬细胞中的存活和复制。因此，我们使用新生隐球菌变种研究了单核巨噬细胞和隐球菌PLB在小鼠模型中传播感染中的作用。Grubii野生型菌株H99、PLBI缺失突变体(Deltaplb1)和重组菌株(Deltaplb1(Rec))。PLB促进了气管内给药的隐球菌进入肺IM。从肺到区域淋巴结的淋巴扩散和进入血液也需要PLB。在H99和Aplb1(Rec)感染的小鼠肺门淋巴结的淋巴窦中可以看到含有萌芽隐球菌的朗汉斯型巨细胞，这表明它们可能在隐球菌感染的传播中起作用。通过尾静脉注射将感染的肺巨噬细胞转移到受体小鼠，证明了这些细胞可以促进隐球菌的血源性传播到大脑，而不依赖于隐球菌的PLB分泌。从肺巨噬细胞或感染脑组织中分离的隐球菌的PLB活性并未持续升高。我们的结论是，单核巨噬细胞是隐球菌传播的媒介，PLB活性是引发间质性肺部感染以及通过淋巴管和血液从肺传播所必需的。然而，当隐球菌出现在单核吞噬细胞内或穿过单核吞噬细胞后，原球蛋白对神经感染的建立并不是必不可少的。
Secreted phospholipase B (PLB) activity promotes the survival and replication of Cryptococcus neoformans in macrophages in vitro. We therefore investigated the role of mononuclear phagocytes and cryptococcal PLB in the dissemination of infection in a mouse model, using C. neoformans var. grubii wild-type strain H99, a PLBI deletion mutant (Deltaplb1), and a reconstituted strain (Deltaplb1(rec)). PLB facilitated the entry of endotracheally administered cryptococci into lung IM. PLB was also required for lymphatic spread from the lung to regional lymph nodes and for entry into the blood. Langhans-type giant cells containing budding cryptococci were seen free in the lymphatic sinuses of hilar nodes of H99- and Aplb1(rec)-infected mice, suggesting that they may have a role in the dissemination of cryptococcal infection. The transfer of infected lung macrophages to recipient mice by tail vein injections demonstrated that these cells can facilitate hematogenous dissemination of cryptococci to the brain, independent of cryptococcal PLB secretion. PLB activities of cryptococci isolated from lung macrophages or infected brains were not persistently increased. We conclude that mononuclear phagocytes are a vehicle for cryptococcal dissemination and that PLB activity is necessary for the initiation of interstitial pulmonary infections and for dissemination from the lung via the lymphatics and blood. PLB is not, however, essential for the establishment of neurological infections when cryptococci are presented within, or after passage through, mononuclear phagocytes.