Kang Tae Jin, Fenton Matthew J, Weiner Matthew A, Hibbs Stephen, Basu Subhendu, Baillie Les, Cross Alan S
Center for Vaccine Development, Department of Medicine, University of Maryland, 685 W. Baltimore Street, HSF I-480, Baltimore, MD 21201,USA.
Infect Immun. 2005 Nov;73(11):7495-501. doi: 10.1128/IAI.73.11.7495-7501.2005.
Anti-protective antigen antibody was reported to enhance macrophage killing of ingested Bacillus anthracis spores, but it was unclear whether the antibody-mediated macrophage killing mechanism was directed against the spore itself or the vegetative form emerging from the ingested and germinating spore. To address this question, we compared the killing of germination-proficient (gp) and germination-deficient (DeltagerH) Sterne 34F2 strain spores by murine peritoneal macrophages. While macrophages similarly ingested both spores, only gp Sterne was killed at 5 h (0.37 log kill). Pretreatment of macrophages with gamma interferon (IFN-gamma) or opsonization with immunoglobulin G (IgG) isolated from a subject immunized with an anthrax vaccine enhanced the killing of Sterne to 0.49 and 0.73 log, respectively, but the combination of IFN-gamma and IgG was no better than either treatment alone. Under no condition was there killing of DeltagerH spores. To examine the ability of the exosporium to protect spores from macrophages, we compared the macrophage-mediated killing of nonsonicated (exosporium+) and sonicated (exosporium-) Sterne 34F2 spores. More sonicated spores than nonsonicated spores were killed at 5 h (0.98 versus 0.37 log kill, respectively). Pretreatment with IFN-gamma increased the sonicated spore killing to 1.39 log. However, the opsonization with IgG was no better than no treatment or pretreatment with IFN-gamma. We conclude that macrophages appear unable to kill the spore form of B. anthracis and that the exosporium may play a role in the protection of spores from macrophages.
据报道,抗保护性抗原抗体可增强巨噬细胞对摄入的炭疽芽孢杆菌孢子的杀伤作用,但尚不清楚抗体介导的巨噬细胞杀伤机制是针对孢子本身还是针对从摄入并萌发的孢子中产生的营养体形式。为了解决这个问题,我们比较了小鼠腹腔巨噬细胞对具有萌发能力(gp)和缺乏萌发能力(DeltagerH)的斯特恩34F2菌株孢子的杀伤情况。虽然巨噬细胞对两种孢子的摄取情况相似,但仅gp斯特恩孢子在5小时时被杀伤(0.37个对数级的杀伤)。用γ干扰素(IFN-γ)预处理巨噬细胞或用从接种炭疽疫苗的受试者中分离的免疫球蛋白G(IgG)进行调理,可分别将斯特恩孢子的杀伤率提高到0.49和0.73个对数级,但IFN-γ和IgG联合使用并不比单独使用任何一种处理效果更好。在任何情况下,DeltagerH孢子均未被杀伤。为了研究芽孢外壁保护孢子免受巨噬细胞杀伤的能力,我们比较了巨噬细胞对未超声处理(有芽孢外壁+)和超声处理(无芽孢外壁-)的斯特恩34F2孢子的杀伤情况。在5小时时,被杀伤的超声处理孢子比未超声处理的孢子更多(分别为0.98和0.37个对数级的杀伤)。用IFN-γ预处理可将超声处理孢子的杀伤率提高到1.39个对数级。然而,用IgG进行调理并不比不处理或用IFN-γ预处理效果更好。我们得出结论,巨噬细胞似乎无法杀伤炭疽芽孢杆菌的孢子形式,并且芽孢外壁可能在保护孢子免受巨噬细胞杀伤方面发挥作用。