Fasciola hepatica infection reduces Mycobacterium bovis burden and mycobacterial uptake and suppresses the pro-inflammatory response.

Fasciola hepatica infection reduces Mycobacterium bovis burden and mycobacterial uptake and suppresses the pro-inflammatory response.
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DOI:
10.1111/pim.12326
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发表时间:
2016-07
影响因子:
2.2
通讯作者:
Mulcahy G
Mulcahy G
中科院分区:
医学4区
文献类型:
--
作者:
Garza-Cuartero L;O'Sullivan J;Blanco A;McNair J;Welsh M;Flynn RJ;Williams D;Diggle P;Cassidy J;Mulcahy G

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由牛分枝杆菌引起的牛结核病(BTB)在爱尔兰共和国和英国的年发病率分别为0.5%和4.7%,尽管有长期的根除计划。未能实现彻底根除是多因素的,但诊断试验的局限性是显著的复杂因素。此前,我们已经证明,在这些地区高度流行的肝片吸虫感染导致合并感染肝片吸虫和牛分枝杆菌的动物的BTB标准诊断试验的敏感性降低。伴随而来的是牛分枝杆菌特异性Th1免疫反应的减少。我们假设,在共同感染的动物中,这些变化将伴随着牛分枝杆菌的增强生长。然而,我们在这里表明,在合并感染肝片吸虫的动物中,牛的分枝杆菌负担减少。此外,我们还证明,感染肝吸虫的牛血单核细胞来源的巨噬细胞(MDM)中分枝杆菌的回收率和摄取率较低,这与抑制促炎细胞因子和转换为巨噬细胞的替代激活有关。然而,感染肝片吸虫的牛MDM中TLR2和CD14的细胞表面表达增加。这些发现反映了蠕虫诱导的促炎反应下调的旁观者效应,为理解合并感染中宿主与病原体的相互作用提供了见解。
Bovine tuberculosis (BTB), caused by Mycobacterium bovis, has an annual incidence in cattle of 0.5% in the Republic of Ireland and 4.7% in the UK, despite long‐standing eradication programmes being in place. Failure to achieve complete eradication is multifactorial, but the limitations of diagnostic tests are significant complicating factors. Previously, we have demonstrated that Fasciola hepatica infection, highly prevalent in these areas, induced reduced sensitivity of the standard diagnostic tests for BTB in animals co‐infected with F. hepatica and M. bovis. This was accompanied by a reduced M. bovis‐specific Th1 immune response. We hypothesized that these changes in co‐infected animals would be accompanied by enhanced growth of M. bovis. However, we show here that mycobacterial burden in cattle is reduced in animals co‐infected with F. hepatica. Furthermore, we demonstrate a lower mycobacterial recovery and uptake in blood monocyte‐derived macrophages (MDM) from F. hepatica‐infected cattle which is associated with suppression of pro‐inflammatory cytokines and a switch to alternative activation of macrophages. However, the cell surface expression of TLR2 and CD14 in MDM from F. hepatica‐infected cattle is increased. These findings reflecting the bystander effect of helminth‐induced downregulation of pro‐inflammatory responses provide insights to understand host‐pathogen interactions in co‐infection.
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