title: Infection of human alveolar macrophages by human coronavirus strain 229E.
abstract: 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-α), regulated on activation normal T-cell expressed and secreted (RANTES/CCL5) and macrophage inflammatory protein 1β (MIP-1β/CCL4) in response to HCoV-229E infection, but these cells exhibited no detectable increase in IFN-β or interleukin-29 in mRNA levels. AMs from smokers had reduced secretion of TNF-α 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.
authors.affiliation: National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.
authors.forename: C Joel
authors.initials: CJ
authors.lastname: Funk
authors.affiliation: National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.
authors.forename: Jieru
authors.initials: J
authors.lastname: Wang
authors.affiliation: National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ito
authors.affiliation: National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.
authors.forename: Emily A
authors.initials: EA
authors.lastname: Travanty
authors.affiliation: National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.
authors.forename: Dennis R
authors.initials: DR
authors.lastname: Voelker
authors.affiliation: Department of Microbiology, University of Colorado Denver, Aurora, CO 80045, USA.
authors.forename: Kathryn V
authors.initials: KV
authors.lastname: Holmes
authors.affiliation: National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Mason
mesh_terms: D002478:Cells, Cultured; D028941:Coronavirus 229E, Human / Q000472:pathogenicity*; D016207:Cytokines / Q000096:biosynthesis / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D004847:Epithelial Cells / Q000821:virology; D019085:Fluorescent Antibody Technique, Direct; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D016676:Macrophages, Alveolar / Q000276:immunology / Q000821:virology*; D010948:Viral Plaque Assay
chemical_list: D016207:Cytokines
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