Abstract：
Ascaris is one of the most widespread helminth infections, leading to chronic morbidity in humans and considerable economic losses in pig farming. In addition, pigs are an important reservoir for the zoonotic salmonellosis, where pigs can serve as asymptomatic carriers. Here, we investigated the impact of an ongoing Ascaris infection on the immune response to Salmonella in pigs. We observed higher bacterial burdens in experimentally coinfected pigs compared to pigs infected with Salmonella alone. The impaired control of Salmonella in the coinfected pigs was associated with repressed interferon gamma responses in the small intestine and with the alternative activation of gut macrophages evident in elevated CD206 expression. Ascaris single and coinfection were associated with a rise of CD4-CD8α+FoxP3+ Treg in the lymph nodes draining the small intestine and liver. In addition, macrophages from coinfected pigs showed enhanced susceptibility to Salmonella infection in vitro and the Salmonella-induced monocytosis and tumor necrosis factor alpha production by myeloid cells was repressed in pigs coinfected with Ascaris. Hence, our data indicate that acute Ascaris infection modulates different immune effector functions with important consequences for the control of tissue-invasive coinfecting pathogens.IMPORTANCEIn experimentally infected pigs, we show that an ongoing infection with the parasitic worm Ascaris suum modulates host immunity, and coinfected pigs have higher Salmonella burdens compared to pigs infected with Salmonella alone. Both infections are widespread in pig production and the prevalence of Salmonella is high in endemic regions of human Ascariasis, indicating that this is a clinically meaningful coinfection. We observed the type 2/regulatory immune response to be induced during an Ascaris infection correlates with increased susceptibility of pigs to the concurrent bacterial infection.
摘要：
蛔虫是最普遍的蠕虫感染之一，导致人类慢性发病率和养猪业的巨大经济损失。此外,猪是人畜共患沙门氏菌病的重要蓄水池，猪可以作为无症状携带者。这里,我们研究了持续的蛔虫感染对猪对沙门氏菌免疫应答的影响.与仅感染沙门氏菌的猪相比，我们观察到实验共感染的猪的细菌负荷更高。合并感染的猪中沙门氏菌的控制受损与小肠中干扰素γ反应的抑制以及在CD206表达升高中明显的肠巨噬细胞的替代激活有关。蛔虫单一和合并感染与小肠和肝脏引流淋巴结中CD4-CD8αFoxP3Treg升高有关。此外,来自共感染猪的巨噬细胞在体外显示出对沙门氏菌感染的敏感性增强，并且在共感染A虫的猪中，沙门氏菌诱导的单核细胞增多和骨髓细胞产生的肿瘤坏死因子α被抑制。因此，我们的数据表明,急性蛔虫感染调节不同的免疫效应功能,对控制组织侵袭性合并感染病原体具有重要作用.IMPORTANCEIN实验感染的猪，我们表明，寄生虫的持续感染会调节宿主的免疫力，与仅感染沙门氏菌的猪相比，共感染的猪的沙门氏菌负担更高。这两种感染在养猪生产中都很普遍，沙门氏菌的流行率在人类a虫病的流行地区很高，表明这是一种有临床意义的合并感染。我们观察到在A虫感染期间诱导的2型/调节性免疫应答与猪对并发细菌感染的易感性增加相关。
