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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 IFN? 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 IFN?. 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 IFN? 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.

SUBMITTER: Cooper GE

PROVIDER: S-EPMC5049764 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Viral Inhibition of Bacterial Phagocytosis by Human Macrophages: Redundant Role of CD36.

Cooper Grace E GE Pounce Zoe C ZC Wallington Joshua C JC Bastidas-Legarda Leidy Y LY Nicholas Ben B Chidomere Chiamaka C Robinson Emily C EC Martin Kirstin K Tocheva Anna S AS Christodoulides Myron M Djukanovic Ratko R Wilkinson Tom M A TM Staples Karl J KJ

PloS one 20161004 10

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 monocy ...[more]

PMID: 27701435

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Project description:BackgroundChronic alcohol consumption impairs alveolar macrophage's (AM) function and increases risk for developing lung infection and pneumonia. However, the mechanism and metabolic basis of alcohol-induced AM dysfunction leading to lung infection are not well defined, but may include altered ethanol (EtOH) and reactive oxygen species metabolism and cellular energetics. Therefore, oxidative stress, endoplasmic reticulum (ER) stress, the formation of fatty acid ethyl esters [FAEEs, nonoxidative metabolites of EtOH], AMP-activated protein kinase (AMPK) signaling, and phagocytic function were examined in freshly isolated AM incubated with EtOH.MethodsAMs separated from bronchoalveolar lavage fluid samples obtained from normal volunteers were incubated with EtOH for 24 hours. AMPK signaling and ER stress were assessed using Western blotting, FAEEs by GC-MS, oxidative stress by immunofluorescence using antibodies to 4-hydroxynonenal, and phagocytosis by latex beads. Oxidative stress was also measured in EtOH-treated AMs with/without AMPK activator [5-aminoimidazole-4-carboxamide ribonucleotide (AICAR)] or inhibitor (Compound C), and in AMs incubated with FAEEs. mRNA expression for interleukins (IL-6 and IL-8), monocyte chemoattractant protein (MCP)-1, and transforming growth factor (TGF)-β was measured in AM treated with EtOH or FAEEs using RT-PCR.ResultsEtOH exposure to AM increased oxidative stress, ER stress, and synthesis of FAEEs, decreased phosphorylated AMPK, and impaired phagocytosis. Attenuation or exacerbation of EtOH-induced oxidative stress by AICAR or Compound C, respectively, suggests a link between AMPK signaling, EtOH metabolism, and related oxidative stress. The formation of FAEEs may contribute to EtOH-induced oxidative stress as FAEEs also produced concentration-dependent oxidative stress. An increased mRNA expression of IL-6, IL-8, and MCP-1 by FAEEs is key finding to suggest a metabolic basis of EtOH-induced inflammatory response.ConclusionsEtOH-induced impaired phagocytosis, oxidative stress, ER stress, and dysregulated AMPK signaling are plausibly associated with the formation of FAEEs and may participate in the pathogenesis of nonspecific pulmonary inflammation.

Dataset Information

Viral Inhibition of Bacterial Phagocytosis by Human Macrophages: Redundant Role of CD36.

Publications

Viral Inhibition of Bacterial Phagocytosis by Human Macrophages: Redundant Role of CD36.

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