Godoy Luiz Claudio, Mariano Mario, Lopes José Daniel
Discipline of Immunology, Department of Microbiology, Immunology and Parasitology, Federal University of São Paulo, SP, Brazil.
Med Mycol. 2003 Oct;41(5):427-36. doi: 10.1080/1369378031000147476.
Pathogenic mechanisms underlying paracoccidioidomycosis are still poorly understood. A well-established murine model of resistance (mouse lineage A/Sn) and susceptibility (lineage B10.A) to P. brasiliensis pulmonary infection was here employed to compare immune response to gp43, the major antigenic component of the fungus. Mice were infected and their cellular and humoral immunity to gp43 were investigated for up to 16 weeks. In both mouse strains, challenge with gp43 indistinguishably evoked a typical immediate-hypersensitivity response, followed by a 24-h late-phase reaction consistent with the same type of immunological activation. IL-4 was detected in cultures of gp43-stimulated lymph node cells only in susceptible animals 2 weeks post-infection, while IL-5 was found throughout the study in both mouse strains. IL-10 appeared in the supernatants of stimulated cells from resistant and susceptible animals in increasing amounts as infection advanced. Conversely, interferon (IFN)-gamma was produced under gp43 stimulation only by cells from A/Sn animals. The humoral response was characterized by low levels of anti-gp43. Titration of IgG isotypes, however, revealed a predominance of IgG1. IgG2a levels were highest in resistant animals, whereas IgG2b levels were highest in susceptible mice. In conclusion, immunity induced by gp43 exhibits common features in A/Sn and B10.A phenotypes, such as immediate hypersensitivity, late phase reaction and high levels of IL-10, but some differences between the strains are also seen.
副球孢子菌病的致病机制仍未完全清楚。本文采用一种成熟的对巴西副球孢子菌肺部感染具有抗性(A/Sn小鼠品系)和易感性(B10.A小鼠品系)的小鼠模型,比较对该真菌主要抗原成分gp43的免疫反应。小鼠受到感染,并对其针对gp43的细胞免疫和体液免疫进行长达16周的研究。在两种小鼠品系中,用gp43攻击均无差别地引发典型的速发型超敏反应,随后是与同一类型免疫激活一致的24小时迟发型反应。仅在感染后2周的易感动物中,在gp43刺激的淋巴结细胞培养物中检测到IL-4,而在整个研究过程中,在两种小鼠品系中均发现了IL-5。随着感染进展,来自抗性和易感动物的刺激细胞上清液中IL-10的含量逐渐增加。相反,仅A/Sn动物的细胞在gp43刺激下产生干扰素(IFN)-γ。体液反应的特征是抗gp43水平较低。然而,IgG同种型的滴定显示IgG1占优势。IgG2a水平在抗性动物中最高,而IgG2b水平在易感小鼠中最高。总之,gp43诱导的免疫在A/Sn和B10.A表型中表现出共同特征,如速发型超敏反应、迟发型反应和高水平的IL-10,但也可见品系之间的一些差异。