巨噬细胞被怀疑参与 1 型糖尿病的发病机制。研究了巨噬细胞在柯萨奇病毒 B4 (CVB4) 向胰腺细胞的传播以及这些细胞的改变中的作用。从外周血分离的人单核细胞用M-CSF（M-CSF巨噬细胞）或GM-CSF（GM-CSF巨噬细胞）分化为巨噬细胞。 M-CSF巨噬细胞接种CVB4。 M-CSF 和 GM-CSF 巨噬细胞被脂多糖和干扰素 (IFN)-γ 激活。将人胰腺β细胞1.1B4用源自M-CSF巨噬细胞的CVB4接种或与CVB4感染的M-CSF巨噬细胞共培养。评估了巨噬细胞培养物中合成分子的抗病毒活性。将活化的巨噬细胞与CVB4持续感染的1.1B4细胞共培养，并测定这些细胞的特异性裂解。我们的研究表明，CVB4 可以感染 M-CSF 巨噬细胞，导致白细胞介素 6 和肿瘤坏死因子 α 以及后来的 IFN-α 的释放。 M-CSF巨噬细胞衍生的CVB4可以感染1.1B4细胞，然后对其进行改变；然而，当这些细胞在含有琼脂糖的培养基中培养时，细胞层没有改变。氟西汀和 CUR-N373 可以抑制巨噬细胞培养物中的 CVB4 复制。活化的 M-CSF 和 GM-CSF 巨噬细胞培养物的上清液诱导 CVB4 持续感染的 1.1B4 细胞裂解。活化的GM-CSF巨噬细胞对CVB4持续感染的1.1B4细胞的细胞溶解活性高于模拟感染的1.1B4细胞。总之，巨噬细胞可能在 CVB4 感染胰腺细胞中发挥作用，并且能够诱导受感染胰腺细胞裂解。© 2024 作者。 《医学病毒学杂志》由 Wiley periodicals LLC 出版。

Macrophages are suspected to be involved in the pathogenesis of type 1 diabetes. The role of macrophages in the transmission of coxsackievirus B4 (CVB4) to pancreatic cells and in the alteration of these cells was investigated. Human monocytes isolated from peripheral blood were differentiated into macrophages with M-CSF (M-CSF macrophages) or GM-CSF (GM-CSF macrophages). M-CSF macrophages were inoculated with CVB4. M-CSF and GM-CSF macrophages were activated with lipopolysaccharide and interferon (IFN)-γ. Human pancreatic beta cells 1.1B4 were inoculated with CVB4 derived from M-CSF macrophages or were cocultured with CVB4-infected M-CSF macrophages. The antiviral activity of synthetic molecules in macrophage cultures was evaluated. Activated macrophages were cocultured with CVB4-persistently infected 1.1B4 cells, and the specific lysis of these cells was determined. Our study shows that CVB4 can infect M-CSF macrophages, leading to the release of interleukin-6 and tumor necrosis factor-α and later IFN-α. M-CSF macrophage-derived CVB4 can infect 1.1B4 cells, which were then altered; however, when these cells were cultured in medium containing agarose, cell layers were not altered. Fluoxetine and CUR-N373 can inhibit CVB4 replication in macrophage cultures. Supernatants of activated M-CSF and GM-CSF macrophage cultures induced lysis of CVB4-persistently infected 1.1B4 cells. The cytolytic activity of activated GM-CSF macrophages was higher towards CVB4-persistently infected 1.1B4 cells than mock-infected 1.1B4 cells. In conclusion, macrophages may play a role in CVB4 infection of pancreatic cells, and are capable of inducing lysis of infected pancreatic cells.© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.