Santangelo Rosemary, Zoellner Hans, Sorrell Tania, Wilson Christabel, Donald Christine, Djordjevic Julianne, Shounan Yi, Wright Lesley
Centre for Infectious Diseases and Microbiology, University of Sydney at Westmead and Department of Infectious Diseases, Westmead Hospital, NSW 2145, Australia.
Infect Immun. 2004 Apr;72(4):2229-39. doi: 10.1128/IAI.72.4.2229-2239.2004.
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 PLB1 deletion mutant (Delta plb1), and a reconstituted strain (Delta plb1(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 Delta plb1(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.
分泌型磷脂酶B（PLB）活性可促进新型隐球菌在体外巨噬细胞中的存活和复制。因此，我们使用新型隐球菌变种格鲁比野生型菌株H99、PLB1缺失突变体（Δplb1）和重组菌株（Δplb1(rec)），研究了单核吞噬细胞和隐球菌PLB在小鼠模型感染传播中的作用。PLB促进气管内给予的隐球菌进入肺间质巨噬细胞。从肺到区域淋巴结的淋巴扩散以及进入血液也需要PLB。在感染H99和Δplb1(rec)的小鼠肺门淋巴结的淋巴窦中可见含有出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体内表明，这些细胞可促进隐球菌经血行扩散至脑，这与隐球菌PLB分泌无关。从肺巨噬细胞或感染脑部分离的隐球菌的PLB活性并未持续增加。我们得出结论，单核吞噬细胞是隐球菌传播的载体，PLB活性对于间质性肺部感染的起始以及从肺通过淋巴管和血液的传播是必需的。然而，当隐球菌存在于单核吞噬细胞内或通过单核吞噬细胞后，PLB对于神经感染的建立并非必不可少。
