Hill J O, Aguirre K M
Trudeau Institute, Inc., Saranac Lake, NY 12983.
J Immunol. 1994 Mar 1;152(5):2344-50.
In immunodeficient hosts, a failure in defense mechanisms allows Cryptococcus neoformans to establish foci of infection in the brain. Immune and nonspecific responses in the primary site of infection in the lung have been described, but those extrapulmonary defense mechanisms that can be mobilized against the yeast have received little attention. This paper describes a response expressed against yeast in the brain of immunocompetent hosts, a response that is weakened in hosts deficient in CD4+ T cells. When a small number of yeast gain access to the vasculature, for example through an i.v. injection, about 0.1% establish themselves in the brain. Normal mice but not SCID mice have the capacity to suppress the multiplication of these yeast cells. The host response is accelerated in mice that are recovering from a primary lung infection, resulting in long term survival without antibiotic chemotherapy. This response is ablated by anti-CD4 mAb treatment and CD4+ cells obtained from infected primed donors are needed to confer immunity on SCID recipients. The critical target for the anti-Cryptococcus immune response are yeast in the brain cortex. However, rather than preventing the colonization of the brain by blood-borne yeast, immunity apparently serves to restrict the growth of yeast in a small number of established foci.
在免疫缺陷宿主中，防御机制的失效使得新型隐球菌能够在脑部形成感染灶。肺部感染原发部位的免疫和非特异性反应已有描述，但针对该酵母菌可调动的肺外防御机制却很少受到关注。本文描述了免疫健全宿主脑部针对酵母菌的一种反应，这种反应在CD4+ T细胞缺陷的宿主中会减弱。当少量酵母菌通过静脉注射等方式进入脉管系统时，约0.1%会在脑部定植。正常小鼠而非严重联合免疫缺陷（SCID）小鼠有能力抑制这些酵母菌细胞的增殖。在从原发性肺部感染中恢复的小鼠中，宿主反应会加速，从而在不进行抗生素化疗的情况下实现长期存活。这种反应可通过抗CD4单克隆抗体治疗消除，且需要从感染致敏供体获得的CD4+细胞来赋予SCID受体免疫力。抗新型隐球菌免疫反应的关键靶点是大脑皮质中的酵母菌。然而，免疫显然不是阻止血源酵母菌在脑部定植，而是限制少量已形成病灶中的酵母菌生长。
