Alidjinou Enagnon Kazali, Sané Famara, Trauet Jacques, Copin Marie-Christine, Hober Didier
Laboratoire de virologie EA3610, Faculté de Médecine, Université de Lille, CHU de Lille 59037, France.
Laboratoire d'immunologie, Faculté de Médecine, Université de Lille, CHU de Lille 59037, France.
Viruses. 2015 Nov 24;7(11):6067-79. doi: 10.3390/v7112924.
Beyond acute infections, group B coxsackieviruses (CVB) are also reported to play a role in the development of chronic diseases, like type 1 diabetes. The viral pathogenesis mainly relies on the interplay between the viruses and innate immune response in genetically-susceptible individuals. We investigated the interaction between CVB4 and macrophages considered as major players in immune response. Monocyte-derived macrophages (MDM) generated with either M-CSF or GM-CSF were inoculated with CVB4, and infection, inflammation, viral replication and persistence were assessed. M-CSF-induced MDM, but not GM-CSF-induced MDM, can be infected by CVB4. In addition, enhancing serum was not needed to infect MDM in contrast with parental monocytes. The expression of viral receptor (CAR) mRNA was similar in both M-CSF and GM-CSF MDM. CVB4 induced high levels of pro-inflammatory cytokines (IL-6 and TNFα) in both MDM populations. CVB4 effectively replicated and persisted in M-CSF MDM, but IFNα was produced in the early phase of infection only. Our results demonstrate that CVB4 can replicate and persist in MDM. Further investigations are required to determine whether the interaction between the virus and MDM plays a role in the pathogenesis of CVB-induced chronic diseases.
除了急性感染外，据报道B组柯萨奇病毒（CVB）在慢性疾病（如1型糖尿病）的发展中也起作用。病毒发病机制主要依赖于病毒与遗传易感个体中固有免疫反应之间的相互作用。我们研究了CVB4与被视为免疫反应主要参与者的巨噬细胞之间的相互作用。用M-CSF或GM-CSF产生的单核细胞衍生巨噬细胞（MDM）接种CVB4，并评估感染、炎症、病毒复制和持续性。M-CSF诱导的MDM可被CVB4感染，而GM-CSF诱导的MDM则不能。此外，与原代单核细胞不同，感染MDM不需要增强血清。病毒受体（CAR）mRNA在M-CSF和GM-CSF MDM中的表达相似。CVB4在两种MDM群体中均诱导高水平的促炎细胞因子（IL-6和TNFα）。CVB4在M-CSF MDM中有效复制并持续存在，但仅在感染早期产生IFNα。我们的结果表明CVB4可以在MDM中复制并持续存在。需要进一步研究以确定病毒与MDM之间的相互作用是否在CVB诱导的慢性疾病发病机制中起作用。
