Laboratoire de Parasitologie, Faculté de Médecine, Université Libre de Bruxelles (ULB), Brussels, Belgium.
PLoS Negl Trop Dis. 2009 Dec 22;3(12):e571. doi: 10.1371/journal.pntd.0000571.
We previously showed that newborns congenitally infected with Trypanosoma cruzi (M+B+) display a strong type 1 parasite-specific T cell immune response, whereas uninfected newborns from T. cruzi-infected mothers (M+B-) are prone to produce higher levels of proinflammatory cytokines than control neonates (M-B-). The purpose of the present study was to determine if such fetal/neonatal immunological environments could alter the response to standard vaccines administered in early life.
Infants (6-7 months old) living in Bolivia, an area highly endemic for T. cruzi infection, and having received Bacillus Calmette Guerin (BCG), hepatitis B virus (HBV), diphtheria and tetanus vaccines, were enrolled into the M+B+, M+B-, M-B- groups mentioned above. The production of IFN-gamma and IL-13, as markers of Th1 and Th2 responses respectively, by peripherical blood mononuclear cells stimulated with tuberculin purified protein derivative of Mycobacterium tuberculosis (PPD) or the vaccinal antigens HBs, diphtheria toxoid (DT) or tetanus toxoid (TT), as well as circulating levels of IgG antibodies against HBsAg, DT and TT were analyzed in infants. Cellular responses to the superantigen SEB were also monitored in M+B+, M+B-, M-B-infants and newborns.
M+B+ infants developed a stronger IFN-gamma response to hepatitis B, diphtheria and tetanus vaccines than did M+B- and M-B- groups. They also displayed an enhanced antibody production to HBsAg. This was associated with a type 1-biased immune environment at birth, since cells of M+B+ newborns produced higher IFN-gamma levels in response to SEB. M+B- infants produced more IFN-gamma in response to PPD than the other groups. IL-13 production remained low and similar in all the three groups, whatever the subject's ages or vaccine status.
These results show that: i) both maternal infection with T. cruzi and congenital Chagas disease do not interfere with responses to BCG, hepatitis B, diphtheria and tetanus vaccines in the neonatal period, and ii) the overcoming of immunological immaturity by T. cruzi infection in early life is not limited to the development of parasite-specific immune responses, but also tends to favour type 1 immune responses to vaccinal antigens.
我们之前曾表明，先天性感染克氏锥虫（M+B+）的新生儿会表现出强烈的寄生虫特异性 1 型 T 细胞免疫反应，而感染克氏锥虫的母亲所生的未感染新生儿（M+B-）则容易比对照新生儿（M-B-）产生更高水平的促炎细胞因子。本研究的目的是确定这种胎儿/新生儿免疫环境是否会改变在生命早期接种标准疫苗后的反应。
生活在玻利维亚的婴儿（6-7 个月大），该地区高度流行克氏锥虫感染，已接种卡介苗（BCG）、乙型肝炎病毒（HBV）、白喉和破伤风疫苗，被纳入上述 M+B+、M+B-、M-B-组。外周血单个核细胞在结核菌素纯化蛋白衍生物（PPD）或疫苗抗原 HBs、白喉类毒素（DT）或破伤风类毒素（TT）刺激下产生 IFN-γ和 IL-13，作为 Th1 和 Th2 反应的标志物分别以及针对 HBsAg、DT 和 TT 的 IgG 抗体的循环水平在婴儿中进行了分析。也监测了 M+B+、M+B-、M-B-婴儿和新生儿对超抗原 SEB 的细胞反应。
与 M+B-和 M-B-组相比，M+B+婴儿对乙型肝炎、白喉和破伤风疫苗的 IFN-γ反应更强。他们对 HBsAg 的抗体产生也增强了。这与出生时的 1 型免疫环境有关，因为 M+B+新生儿的细胞对 SEB 的反应产生了更高水平的 IFN-γ。与其他两组相比，M+B-婴儿对 PPD 的 IFN-γ产生更多。所有三组的 IL-13 产生均保持较低且相似，无论受试者的年龄或疫苗状态如何。
这些结果表明：i）母体感染克氏锥虫和先天性恰加斯病都不干扰新生儿期对 BCG、乙型肝炎、白喉和破伤风疫苗的反应，ii）克氏锥虫感染对早期生命中免疫不成熟的克服不仅限于寄生虫特异性免疫反应的发展，而且还倾向于有利于对疫苗抗原的 1 型免疫反应。
