Wright Lesley, Bubb William, Davidson John, Santangelo Rosemary, Krockenberger Mark, Himmelreich Uwe, Sorrell Tania
Department of Infectious Diseases, Center for Infectious Diseases and Microbiology, Level 3, ICPMR Building, University of Sydney, Westmead Hospital, Westmead, NSW 2145, Australia.
Microbes Infect. 2002 Nov;4(14):1427-38. doi: 10.1016/s1286-4579(02)00024-2.
Differences in the ability of Cryptococcus neoformans var. neoformans (CNVN) and var. gattii (CNVG) to establish localized lesions in the lungs of healthy humans remain unexplained. In this study, CNVG infection in a rat model was characterized by early neutrophil invasion into lung tissue, but phagocytosis of cryptococci was not observed. The chemical composition of non-enzymic components secreted by one strain of each variety (heat-inactivated supernatants from CNVN and CNVG, termed vns and vgs, respectively) were compared, using magnetic resonance spectroscopy. Effects on human neutrophil viability and functions at both pH 5.5 and 7.0 were investigated, as the pH of cryptococcomas was found to be 5.4-5.6 in vivo. The supernatants were similar in composition, although metabolites in vns were generally present in higher concentrations. In addition, vgs contained two novel metabolites-acetoin and dihydroxyacetone. Polyphosphate was observed in cells from both varieties and may be a source of extracellular inorganic phosphate. Superoxide production in the presence of phorbol ester was enhanced by treatment with vns and decreased by vgs. At pH 5.5, vns caused high levels of necrosis in neutrophils, as well as increased adhesion/migration through A549 lung epithelial cell monolayers. Individual supernatant components such as polyols, acetoin, dihydroxyacetone, and gamma-aminobutyric acid exhibited both pro- and anti-inflammatory properties. Overall, we found that vgs was potentially less pro-inflammatory than vns. Inhibition of neutrophil function by products of CNVG may promote survival of extracellular organisms, and local multiplication to form cryptococcomas.
新型隐球菌新生变种（CNVN）和格特变种（CNVG）在健康人类肺部形成局部病灶能力的差异仍未得到解释。在本研究中，大鼠模型中的CNVG感染特征为早期中性粒细胞侵入肺组织，但未观察到隐球菌的吞噬现象。使用磁共振波谱比较了每个变种的一个菌株分泌的非酶成分的化学组成（分别来自CNVN和CNVG的热灭活上清液，称为vns和vgs）。研究了在pH 5.5和7.0时对人中性粒细胞活力和功能的影响，因为体内隐球菌瘤的pH值为5.4 - 5.6。上清液的组成相似，尽管vns中的代谢物浓度通常较高。此外，vgs含有两种新的代谢物——乙偶姻和二羟基丙酮。在两个变种的细胞中均观察到多磷酸盐，它可能是细胞外无机磷酸盐的来源。在用佛波酯处理时，vns增强了超氧化物的产生，而vgs则使其减少。在pH 5.5时，vns导致中性粒细胞高水平坏死，并增加通过A549肺上皮细胞单层的黏附/迁移。多元醇、乙偶姻、二羟基丙酮和γ-氨基丁酸等单个上清液成分表现出促炎和抗炎特性。总体而言，我们发现vgs的促炎潜力可能低于vns。CNVG产物对中性粒细胞功能的抑制可能促进细胞外生物体的存活和局部增殖以形成隐球菌瘤。
