Cham Lamin B, Adomati Tom, Li Fanghui, Ali Murtaza, Lang Karl S
Institute of Immunology, Medical Faculty, University of Duisburg-Essen, Hufelandstr. 55, 45147 Essen, Germany.
Antibodies (Basel). 2020 Sep 1;9(3):44. doi: 10.3390/antib9030044.
The integrin associated protein (CD47) is a widely and moderately expressed glycoprotein in all healthy cells. Cancer cells are known to induce increased CD47 expression. Similar to cancer cells, all immune cells can upregulate their CD47 surface expression during infection. The CD47-SIRPa interaction induces an inhibitory effect on macrophages and dendritic cells (dendritic cells) while CD47-thrombospondin-signaling inhibits T cells. Therefore, the disruption of the CD47 interaction can mediate several biologic functions. Upon the blockade and knockout of CD47 reveals an immunosuppressive effect of CD47 during LCMV, influenza virus, HIV-1, , and other bacterial pneumonia infections. In our recent study we shows that the blockade of CD47 using the anti-CD47 antibody increases the activation and effector function of macrophages, dendritic cells and T cells during viral infection. By enhancing both innate and adaptive immunity, CD47 blocking antibody promotes antiviral effect. Due to its broad mode of action, the immune-stimulatory effect derived from this antibody could be applicable in nonresolving and (re)emerging infections. The anti-CD47 antibody is currently under clinical trial for the treatment of cancer and could also have amenable therapeutic potential against infectious diseases. This review highlights the immunotherapeutic targeted role of CD47 in the infectious disease realm.
整合素相关蛋白（CD47）是一种在所有健康细胞中广泛且适度表达的糖蛋白。已知癌细胞会诱导CD47表达增加。与癌细胞类似，所有免疫细胞在感染期间都能上调其CD47表面表达。CD47-SIRPa相互作用对巨噬细胞和树突状细胞产生抑制作用，而CD47-血小板反应蛋白信号传导则抑制T细胞。因此，CD47相互作用的破坏可介导多种生物学功能。在阻断和敲除CD47后发现，在淋巴细胞性脉络丛脑膜炎病毒、流感病毒、HIV-1及其他细菌性肺炎感染期间，CD47具有免疫抑制作用。在我们最近的研究中，我们发现使用抗CD47抗体阻断CD47可在病毒感染期间增强巨噬细胞、树突状细胞和T细胞的激活及效应功能。通过增强固有免疫和适应性免疫，CD47阻断抗体可促进抗病毒作用。由于其广泛的作用方式，这种抗体产生的免疫刺激作用可能适用于持续性和（再）新发感染。抗CD47抗体目前正在进行治疗癌症的临床试验，也可能具有针对传染病的治疗潜力。本综述强调了CD47在传染病领域的免疫治疗靶向作用。
