Infection of human alveolar macrophages by human coronavirus strain 229E
Infection of human alveolar macrophages by human coronavirus strain 229E
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DOI：
10.1099/vir.0.038414-0
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发表时间：
2012-03-01
影响因子：
3.8
通讯作者：
Mason, Robert J.
中科院分区：
文献类型：
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作者：
Funk, C. Joel;Wang, Jieru;Mason, Robert J.
人类冠状病毒株229 E（HCoV-229 E）通常会引起上呼吸道感染。然而，下呼吸道感染可能发生在一些个体中，表明远端肺中的细胞对HCoV-229 E易感。本研究测定了人肺泡上皮细胞和肺泡巨噬细胞（AM）原代培养物的病毒易感性。荧光抗体染色表明，HCoV-229 E可以很容易地感染AM，但没有证据表明，在分化的肺泡上皮II型细胞中的感染，只有一个非常低的水平，在II型细胞转化为I型样细胞表型的感染。然而，人支气管上皮细胞系（16 HBE）很容易感染。评估AM对HCoV-229 E感染的天然免疫应答的细胞因子产生和干扰素（IFN）基因表达。AM分泌显著量的肿瘤坏死因子α（TNF-α），调节正常T细胞表达和分泌的活化（RANTES/CCL 5）和巨噬细胞炎性蛋白1 β（MIP-1 β/CCL 4）以响应HCoV-229 E感染，但这些细胞在IFN-β或白细胞介素-29的mRNA水平上未表现出可检测的增加。与非吸烟者相比，吸烟者AM对HCoV-229 E感染的TNF-α分泌减少。表面活性蛋白A（SP-A）和SP-D是远端肺中先天免疫系统的一部分。两种表面活性蛋白均与HCoV-229 E结合，并且用SP-A或SP-D预处理HCoV-229 E抑制16 HBE细胞的感染。相比之下，SP-A使AM的感染适度减少，但SP-D没有。总之，AM是HCoV-229 E的重要靶标，并且它们可以对感染产生促炎性先天免疫应答。
Human coronavirus strain 229E (HCoV-229E) commonly causes upper respiratory tract infections. However, lower respiratory tract infections can occur in some individuals, indicating that cells in the distal lung are susceptible to HCoV-229E. This study determined the virus susceptibility of primary cultures of human alveolar epithelial cells and alveolar macrophages (AMs). Fluorescent antibody staining indicated that HCoV-229E could readily infect AMs, but no evidence was found for infection in differentiated alveolar epithelial type II cells and only a very low level of infection in type II cells transitioning to the type I-like cell phenotype. However, a human bronchial epithelial cell line (16HBE) was readily infected. The innate immune response of AMs to HCoV-229E infection was evaluated for cytokine production and interferon (IFN) gene expression. AMs secreted significant amounts of tumour necrosis factor alpha (TNF-alpha), regulated on activation normal T-cell expressed and secreted (RANTES/CCL5) and macrophage inflammatory protein 1 beta (MIP-1 beta/CCL4) in response to HCoV-229E infection, but these cells exhibited no detectable increase in IFN-beta or interleukin-29 in mRNA levels. AMs from smokers had reduced secretion of TNF-alpha compared with non-smokers in response to HCoV-229E infection. Surfactant protein A (SP-A) and SP-D are part of the innate immune system in the distal lung. Both surfactant proteins bound to HCoV-229E, and pre-treatment of HCoV-229E with SP-A or SP-D inhibited infection of 16HBE cells. In contrast, there was a modest reduction in infection in AMs by SP-A, but not by SP-D. In summary, AMs are an important target for HCoV-229E, and they can mount a pro-inflammatory innate immune response to infection.