Biozentrum, University of Basel, Basel, Switzerland.
Division of Experimental Virology, Department of Biomedicine, University of Basel, Basel, Switzerland.
PLoS Pathog. 2022 May 17;18(5):e1010489. doi: 10.1371/journal.ppat.1010489. eCollection 2022 May.
Vertical transmission of Bartonella infection has been reported for several mammalian species including mice and humans. Accordingly, it is commonly held that acquired immunological tolerance contributes critically to the high prevalence of Bartonellae in wild-ranging rodent populations. Here we studied an experimental model of Bartonella infection in mice to assess the impact of maternal and newborn immune defense on vertical transmission and bacterial persistence in the offspring, respectively. Congenital infection was frequently observed in B cell-deficient mothers but not in immunocompetent dams, which correlated with a rapid onset of an antibacterial antibody response in infected WT animals. Intriguingly, B cell-deficient offspring with congenital infection exhibited long-term bacteremia whereas B cell-sufficient offspring cleared bacteremia within a few weeks after birth. Clearance of congenital Bartonella infection resulted in immunity against bacterial rechallenge, with the animals mounting Bartonella-neutralizing antibody responses of normal magnitude. These observations reveal a key role for humoral immune defense by the mother and offspring in preventing and eliminating vertical transmission. Moreover, congenital Bartonella infection does not induce humoral immune tolerance but results in anti-bacterial immunity, questioning the contribution of neonatal tolerance to Bartonella prevalence in wild-ranging rodents.
垂直传播的巴尔通体感染已被报道存在于包括鼠类和人类在内的多种哺乳动物中。因此,人们普遍认为,获得性免疫耐受对于巴尔通体在野生啮齿动物种群中的高流行率起着至关重要的作用。在这里,我们研究了一种在小鼠中感染巴尔通体的实验模型,以分别评估母源和新生免疫防御对垂直传播和细菌持续性的影响。在 B 细胞缺陷的母亲中经常观察到先天性感染,但在免疫功能正常的母体中则没有,这与感染 WT 动物中快速出现的抗细菌抗体反应相关。有趣的是,先天性感染的 B 细胞缺陷后代表现出长期菌血症,而 B 细胞充足的后代在出生后数周内清除菌血症。先天性巴尔通体感染的清除导致对细菌再挑战产生免疫,动物产生正常大小的巴尔通体中和抗体反应。这些观察结果揭示了母源和后代的体液免疫防御在预防和消除垂直传播中的关键作用。此外,先天性巴尔通体感染不会诱导体液免疫耐受,反而会导致抗细菌免疫,这对野生啮齿动物中新生耐受对巴尔通体流行率的贡献提出了质疑。