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

Cooper, Grace E.; Pounce, Zoe C.; Wallington, Joshua C.; Bastidas-Legarda, Leidy; Nicholas, Ben; Chidomere, Chiamaka; Robinson, Emily C.; Martin, Kirstin; Tocheva, Anna S.; Christodoulides, Myron; Djukanović, Ratko; Wilkinson, Tom; Staples, Karl J.

doi:10.1371/journal.pone.0163889

Cited by 20 publications

(18 citation statements)

References 37 publications

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“…To investigate the effects of NK cell activation during IAV infection, we cultured peripheral blood NK cells with IAV-infected autologous MDMs. MDMs were differentiated to a lung-like phenotype, modeling airway macrophage activity and infected as described previously ( 45 ), resulting in a median of 29% of MDMs being positive for viral NP1 (Figure 9 A). Following infection of the MDM monolayer, purified autologous NK cells were cultured with infected MDMs at an E:T ratio of 1:5 for 4–6 h resulting in increased NK cell degranulation ( P = 0.031, Figure 9 B).…”

Section: Resultsmentioning

confidence: 95%

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Human CD49a+ Lung Natural Killer Cell Cytotoxicity in Response to Influenza A Virus

et al. 2018

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Influenza A virus (IAV) is a major global public health burden due to its routine evasion of immunization strategies. Natural killer (NK) cells are innate cytotoxic cells with important antiviral activity in the human body, yet the function of these cells in the control of IAV infection is unclear. The aim of this study was to determine the role of lung NK cell cytotoxic responses to IAV. Human lung explants were infected ex vivo with IAV, and lung NK cell activation was analyzed by flow cytometry. Cytotoxic responses of NK cell subsets against IAV-infected macrophages were measured by flow cytometry and ELISA. Despite reports of hypofunctionality in the pulmonary environment, human lung-associated NK cells responded rapidly to ex vivo IAV infection, with upregulation of surface CD107a 24 h post-infection. The lung NK cell phenotype is similar in maturity and differentiation to NK cells of the peripheral blood but a unique CD56brightCD49a+CD103+CD69+ NK cell population was identified in the lung, indicating NK cell residency within this organ. In response to ex vivo IAV infection a greater proportion of resident CD56brightCD49a+ NK cells expressed surface CD107a compared with CD56brightCD49a− NK cells, suggesting a hyperfunctional NK cell population may be present within human lung tissue and could be the result of innate immunological training. Furthermore, NK cells provided significant antiviral, cytotoxic activity following contact with influenza-infected cells, including the production and release of IFN-γ and granzyme-B resulting in macrophage cell death. These results suggest that a resident, trained NK cell population are present in the human lung and may provide early and important control of viral infection. A greater understanding of this resident mucosal population may provide further insight into the role of these cells in controlling viral infection and generating appropriate adaptive immunity to IAV.

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Section: Resultsmentioning

confidence: 95%

“…Cells isolated from the buffy coat were then stained for flow cytometry. For IAV infection of lung explants, lung fragments were washed in PBS and infected with 200,000 pfu/mL live or UV-irradiated X31 (H3N2) IAV (Virapur) following rest ( 42 , 45 ). UV-irradiated X31 was created by exposing live X31 to UV light for 2 h on ice.…”

Section: Methodsmentioning

confidence: 99%

Human CD49a+ Lung Natural Killer Cell Cytotoxicity in Response to Influenza A Virus

et al. 2018

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“…Likewise, the circulation of respiratory viruses during the winter months, especially the influenza virus, respiratory syncytial virus (RSV), and metapneumovirus, have been associated with an increased incidence of IPD, especially in children (2,7). Although the mechanisms of interaction between respiratory viruses and Streptococcus pneumoniae at the host level have been widely described (8)(9)(10)(11), the proportion of episodes of IPD attributable to the circulation of respiratory viruses is not clear (12,13).…”

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Invasive Pneumococcal Disease and Influenza Activity in a Pediatric Population: Impact of PCV13 Vaccination in Epidemic and Nonepidemic Influenza Periods

et al. 2019

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The objective of this study was to analyze the incidence, clinical presentation, and severity of invasive pneumococcal disease (IPD)-causing serotypes and the impact of the 13-valent pneumococcal conjugate vaccination during epidemic and nonepidemic influenza periods in Catalonia, Spain. This was a prospective study in persons aged <18 years diagnosed with IPD between 2012 and 2015 in three Catalan pediatric hospitals. IPD was defined as clinical infection together with isolation of Streptococcus pneumoniae by culture and/or detection by reverse transcription-PCR in a normally sterile sample. Incidence rate ratios (IRRs) and the fraction of IPD prevented associated with 13-valent pneumococcal conjugate vaccine (PCV13) were calculated. The bivariate analysis used the χ2 test and the multivariate analysis nonconditional logistic regression. A total of 229 cases of IPD were recorded. The incidence was higher during influenza epidemic periods (IRR, 2.7; 95% confidence interval [CI], 2.05 to 3.55; P < 0.001), especially for pneumonia (IRR, 3.25; 95% CI, 2.36 to 4.47; P < 0.001), with no differences in the distribution of pneumococcal serotypes. Complications during admission and sequel at discharge were greater during epidemic periods (adjusted odds ratio [aOR], 2.00; 95% CI, 1.06 to 3.77; P = 0.03) than at nonepidemic periods (aOR, 3.38; 95% CI, 1.37 to 8.29; P = 0.01). The prevented fraction for the population (PFp) of IPD in children aged 7 to 59 months was 48% to 49.4%. The PFp was higher in influenza epidemic than nonepidemic periods and increased when ≥2 doses of PCV13 or ≥1 after 24 months were administered. Influenza virus circulation increases the incidence of IPD in persons aged <18 years. In influenza epidemic periods, IPD cases were more severe. Increased PCV13 coverage might increase the fraction of IPD prevented in epidemic and nonepidemic periods.

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“…Little is known about the effect of HRV infection on macrophage phagocytosis, although recent data suggest other respiratory viruses, such as influenza and respiratory syncytial virus, may decrease bacterial uptake in human macrophages (18). Although previous work has predominantly focused on epithelial cells, which are the primary site of HRV replication (19), HRV may induce distinct transcriptome profiles, which are driven toward a proinflammatory phenotype in polarized human macrophages (20) and to alter the activation status of AM in a mouse model of asthma exacerbations (21).…”

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Human Rhinovirus Impairs the Innate Immune Response to Bacteria in Alveolar Macrophages in Chronic Obstructive Pulmonary Disease

Finney

Belchamber

Fenwick

et al. 2019

Am J Respir Crit Care Med

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Rationale: Human rhinovirus (HRV) is a common cause of chronic obstructive pulmonary disease (COPD) exacerbations. Secondary bacterial infection is associated with more severe symptoms and delayed recovery. Alveolar macrophages clear bacteria from the lung and maintain lung homeostasis through cytokine secretion. These processes are defective in COPD. The effect of HRV on macrophage function is unknown. Objectives: To investigate the effect of HRV on phagocytosis and cytokine response to bacteria by alveolar macrophages and monocyte-derived macrophages (MDM) in COPD and healthy control subjects. Methods: Alveolar macrophages were obtained by bronchoscopy and MDM by adherence. Macrophages were exposed to HRV16 (multiplicity of infection 5), polyinosinic:polycytidylic acid (poly I:C) 30 mg/ml, IFN-b 10 mg/ml, IFN-g 10 mg/ml, or medium control for 24 hours. Phagocytosis of fluorescently labeled Haemophilus influenzae or Streptococcus pneumoniae was assessed by fluorimetry. CXCL8 (IL-8), IL-6, TNF-a (tumor necrosis factor-a), and IL-10 release was measured by ELISA. Measurements and Main Results: HRV significantly impaired phagocytosis of H. influenzae by 23% in MDM (n = 37; P = 0.004) and 18% in alveolar macrophages (n = 20; P , 0.0001) in COPD. HRV also significantly reduced phagocytosis of S. pneumoniae by 33% in COPD MDM (n = 20; P = 0.0192). There was no effect in healthy control subjects. Phagocytosis of H. influenzae was also impaired by poly I:C but not IFN-b or IFN-g in COPD MDM. HRV significantly reduced cytokine responses to H. influenzae. The IL-10 response to H. influenzae was significantly impaired by poly I:C, IFN-b, and IFN-g in COPD cells. Conclusions: HRV impairs phagocytosis of bacteria in COPD, which may lead to an outgrowth of bacteria. HRV also impairs cytokine responses to bacteria via the TLR3/IFN pathway, which may prevent resolution of inflammation leading to prolonged exacerbations in COPD.

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

Cited by 20 publications

References 37 publications

Human CD49a+ Lung Natural Killer Cell Cytotoxicity in Response to Influenza A Virus

Human CD49a+ Lung Natural Killer Cell Cytotoxicity in Response to Influenza A Virus

Invasive Pneumococcal Disease and Influenza Activity in a Pediatric Population: Impact of PCV13 Vaccination in Epidemic and Nonepidemic Influenza Periods

Human Rhinovirus Impairs the Innate Immune Response to Bacteria in Alveolar Macrophages in Chronic Obstructive Pulmonary Disease

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