title: Viral Inhibition of Bacterial Phagocytosis by Human Macrophages: Redundant Role of CD36.
abstract: Macrophages are essential to maintaining lung homoeostasis and recent work has demonstrated that influenza-infected lung macrophages downregulate their expression of the scavenger receptor CD36. This receptor has also been shown to be involved in phagocytosis of Streptococcus pneumoniae, a primary agent associated with pneumonia secondary to viral infection. The aim of this study was to investigate the role of CD36 in the effects of viral infection on macrophage phagocytic function. Human monocyte-derived macrophages (MDM) were exposed to H3N2 X31 influenza virus, M37 respiratory syncytial virus (RSV) or UV-irradiated virus. No infection of MDM was seen upon exposure to UV-irradiated virus but incubation with live X31 or M37 resulted in significant levels of viral detection by flow cytometry or RT-PCR respectively. Infection resulted in significantly diminished uptake of S. pneumoniae by MDM and significantly decreased expression of CD36 at both the cell surface and mRNA level. Concurrently, there was a significant increase in IFNβ gene expression in response to infection and we observed a significant decrease in bacterial phagocytosis (p = 0.031) and CD36 gene expression (p = 0.031) by MDM cultured for 24 h in 50IU/ml IFNβ. Knockdown of CD36 by siRNA resulted in decreased phagocytosis, but this was mimicked by transfection reagent alone. When MDM were incubated with CD36 blocking antibodies no effect on phagocytic ability was observed. These data indicate that autologous IFNβ production by virally-infected cells can inhibit bacterial phagocytosis, but that decreased CD36 expression by these cells does not play a major role in this functional deficiency.
authors.affiliation: Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, United Kingdom.
authors.forename: Grace E
authors.initials: GE
authors.lastname: Cooper
authors.affiliation: Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, United Kingdom.
authors.forename: Zoe C
authors.initials: ZC
authors.lastname: Pounce
authors.affiliation: Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, United Kingdom.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Wallington
authors.affiliation: Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, United Kingdom.
authors.forename: Leidy Y
authors.initials: LY
authors.lastname: Bastidas-Legarda
authors.affiliation: Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, United Kingdom.
authors.forename: Ben
authors.initials: B
authors.lastname: Nicholas
authors.affiliation: Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, United Kingdom.
authors.forename: Chiamaka
authors.initials: C
authors.lastname: Chidomere
authors.affiliation: Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, United Kingdom.
authors.forename: Emily C
authors.initials: EC
authors.lastname: Robinson
authors.affiliation: Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, United Kingdom.
authors.forename: Kirstin
authors.initials: K
authors.lastname: Martin
authors.affiliation: Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, United Kingdom.
authors.forename: Anna S
authors.initials: AS
authors.lastname: Tocheva
authors.affiliation: Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, United Kingdom.
authors.forename: Myron
authors.initials: M
authors.lastname: Christodoulides
authors.affiliation: Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, United Kingdom.|Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, United Kingdom.
authors.forename: Ratko
authors.initials: R
authors.lastname: Djukanovic
authors.affiliation: Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, United Kingdom.|Southampton NIHR Respiratory Biomedical Research Unit, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, United Kingdom.
authors.forename: Tom M A
authors.initials: TM
authors.lastname: Wilkinson
authors.affiliation: Clinical and Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital, Tremona Road, Southampton, SO16 6YD, United Kingdom.
authors.forename: Karl J
authors.identifier: http://orcid.org/0000-0003-3844-6457
authors.initials: KJ
authors.lastname: Staples
mesh_terms: D018955:CD36 Antigens / Q000235:genetics* / Q000378:metabolism*; D002478:Cells, Cultured; D015536:Down-Regulation; D006801:Humans; D009980:Influenza A virus / Q000235:genetics / Q000472:pathogenicity; D016899:Interferon-beta / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology / Q000382:microbiology*; D010587:Phagocytosis; D012328:RNA Viruses / Q000235:genetics / Q000472:pathogenicity*; D012367:RNA, Viral / Q000235:genetics; D012136:Respiratory Syncytial Viruses / Q000235:genetics / Q000472:pathogenicity; D013296:Streptococcus pneumoniae / Q000472:pathogenicity*
chemical_list: D018955:CD36 Antigens; D012367:RNA, Viral; D016899:Interferon-beta