Alveolar-like Macrophages Attenuate Respiratory Syncytial Virus Infection.

Autor:	Porto BN; Program in Translational Medicine, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Litvack ML; Program in Translational Medicine, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Cen Y; Program in Translational Medicine, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada., Lok I; Program in Translational Medicine, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.; Neonatal Intensive Care Unit, Emma Children's Hospital, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands., Bouch S; Program in Translational Medicine, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Norris MJ; Program in Translational Medicine, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.; Center for Infectious Disease and Vaccine Research, La Jolla Institute for Immunology, La Jolla, CA 92037, USA., Duan W; Program in Translational Medicine, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada., Ackerley C; Program in Translational Medicine, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada., Post M; Program in Translational Medicine, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada., Moraes TJ; Program in Translational Medicine, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5S 1A8, Canada.; Division of Respiratory Medicine, Department of Pediatrics, Hospital for Sick Children, Toronto, ON M5G 1X8, Canada.
Jazyk:	angličtina
Zdroj:	Viruses [Viruses] 2021 Sep 29; Vol. 13 (10). Date of Electronic Publication: 2021 Sep 29.
DOI:	10.3390/v13101960
Abstrakt:	Respiratory Syncytial Virus (RSV) is the leading cause of acute lower respiratory infections in young children and infection has been linked to the development of persistent lung disease in the form of wheezing and asthma. Despite substantial research efforts, there are no RSV vaccines currently available and an effective monoclonal antibody targeting the RSV fusion protein (palivizumab) is of limited general use given the associated expense. Therefore, the development of novel approaches to prevent RSV infection is highly desirable to improve pediatric health globally. We have developed a method to generate alveolar-like macrophages (ALMs) from pluripotent stem cells. These ALMs have shown potential to promote airway innate immunity and tissue repair and so we hypothesized that ALMs could be used as a strategy to prevent RSV infection. Here, we demonstrate that ALMs are not productively infected by RSV and prevent the infection of epithelial cells. Prevention of epithelial infection was mediated by two different mechanisms: phagocytosis of RSV particles and release of an antiviral soluble factor different from type I interferon. Furthermore, intratracheal administration of ALMs protected mice from subsequent virus-induced weight loss and decreased lung viral titres and inflammation, indicating that ALMs can impair the pathogenesis of RSV infection. Our results support a prophylactic role for ALMs in the setting of RSV infection and warrant further studies on stem cell-derived ALMs as a novel cell-based therapy for pulmonary viral infections.
Databáze:	MEDLINE
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