Buchanan K L, Murphy J W
Department of Microbiology and Immunology, University of Oklahoma Health Sciences Center, Oklahoma City 73190.
Infect Immun. 1993 Jul;61(7):2854-65. doi: 10.1128/iai.61.7.2854-2865.1993.
Cryptococcosis, an increasingly important opportunistic infection caused by the encapsulated yeast-like organism Cryptococcus neoformans, is limited by an anticryptococcal cell-mediated immune (CMI) response. Gaining a thorough understanding of the complex anticryptococcal CMI response is essential for developing means of controlling infections with C. neoformans. The murine cryptococcosis model utilizing footpad swelling to cryptococcal antigen (delayed-type hypersensitivity [DTH]) has proven to be a valuable tool for studying the induction and regulation of the anticryptococcal CMI response, but this technique has limitations with regard to evaluating the role of the final effector cells recruited by an ongoing CMI response. The purpose of this study was to assess the types of cells and cytokines induced into the site of cryptococcal antigen deposition in C. neoformans-infected and -immunized mice compared with those for control mice. We used a gelatin sponge implant model to examine the cells and cytokines present at the site of an anticryptococcal DTH response. Sponges implanted in infected mice and injected with cryptococcal culture filtrate antigen (CneF) 24 h before assessment had significantly increased numbers of infiltrating leukocytes compared with saline-injected sponges in the same animals. Exaggerated influxes of neutrophils and mononuclear cells were the major contributors to the increase in total numbers of cells in the DTH-reactive sponges. The numbers of CD4+ and LFA-1+ cells were found to be significantly increased in the CneF-injected sponges of infected and immunized mice over the numbers in control sponges. The numbers of large granular lymphocytes were also increased in DTH-reactive sponges compared with control sponges. Gamma interferon, interleukin 2 (IL-2), and IL-5 are clearly relevant cytokines in the anticryptococcal CMI response, since they were produced in greater amounts in the CneF-injected sponges from C. neoformans-infected and -immunized mice than in control sponges. IL-4 was not associated with the expression of DTH to cryptococcal antigen. The gelatin sponge model is an excellent tool for studying cells and cytokines involved in specific CMI responses.
隐球菌病是由包膜酵母样真菌新型隐球菌引起的一种日益重要的机会性感染，受抗隐球菌细胞介导免疫（CMI）反应的限制。深入了解复杂的抗隐球菌CMI反应对于开发控制新型隐球菌感染的方法至关重要。利用足垫对隐球菌抗原肿胀反应（迟发型超敏反应[DTH]）的小鼠隐球菌病模型已被证明是研究抗隐球菌CMI反应诱导和调节的有价值工具，但该技术在评估正在进行的CMI反应募集的最终效应细胞的作用方面存在局限性。本研究的目的是评估与对照小鼠相比，新型隐球菌感染和免疫小鼠中隐球菌抗原沉积部位诱导的细胞类型和细胞因子。我们使用明胶海绵植入模型来检查抗隐球菌DTH反应部位存在的细胞和细胞因子。在评估前24小时植入感染小鼠并注射隐球菌培养滤液抗原（CneF）的海绵，与同一动物中注射生理盐水的海绵相比，浸润白细胞数量显著增加。嗜中性粒细胞和单核细胞的过度流入是DTH反应性海绵中细胞总数增加的主要原因。发现感染和免疫小鼠注射CneF的海绵中CD4 +和LFA - 1 +细胞的数量比对照海绵中的数量显著增加。与对照海绵相比，DTH反应性海绵中大颗粒淋巴细胞的数量也增加。γ干扰素、白细胞介素2（IL - 2）和IL - 5显然是抗隐球菌CMI反应中的相关细胞因子，因为它们在新型隐球菌感染和免疫小鼠注射CneF的海绵中产生的量比对照海绵中更多。IL - 4与对隐球菌抗原的DTH表达无关。明胶海绵模型是研究参与特定CMI反应的细胞和细胞因子的优秀工具。
