Rhinovirus infection induces distinct transcriptome profiles in polarized human macrophages

Rajput, Charu; Walsh, Megan P; Eder, Breanna N.; Metitiri, Ediri E.; Popova, Antonia P.; Hershenson, Marc B.

doi:10.1152/physiolgenomics.00122.2017

Cited by 18 publications

(15 citation statements)

References 58 publications

(58 reference statements)

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“…These findings are in line with a recent study by Rajput, et al . 37 who observed higher responsiveness to rhinovirus infection in M1-primed macrophages compared to M2-primed macrophages, which was associated with higher expression of MDA5. In our study, RV-induced expression of TLR3 was reduced in human M2-like macrophages compared to M1-like ones.…”

Section: Discussionmentioning

confidence: 95%

Rhinovirus-induced IFNβ expression is NFκB-dependent and regulated by the macrophage microenvironment

Menzel

Kosinski

Uller

et al. 2019

Sci Rep

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Macrophages play an important role in asthma pathogenesis both in the inflammatory and resolution phase of the disease. Macrophages can acquire different polarisation states dependent on their microenvironment. It is yet unclear through which mechanism the microenvironment affects the anti-viral response in macrophages. We hypothesized that the macrophage microenvironment regulates rhinovirus-induced IFNβ expression. Murine bone marrow-derived monocytes and human differentiated THP-1 cells were stimulated with M-CSF or GM-CSF and IFNγ or IL-4/IL-13, respectively, to mimic a Th1 or Th2 environment. Macrophages were infected with rhinovirus and gene and protein levels of IFNβ and pattern recognition receptor expression were measured. In subsequent experiments an IκB kinase inhibitor was used to study the involvement of NFκB. Both murine and human M1-like macrophages exhibited higher levels of IFNβ and pattern recognition receptors after rhinovirus infection than M2-like macrophages. Blockage of NFκB resulted in a lower expression of rhinovirus-induced IFNβ in human M1-like macrophages while inducing a higher expression in M2-like macrophages, suggesting that the interferon response towards viral infection was mediated by NFκB. These findings could contribute to a better understanding of mechanisms causing reduced anti-viral responses at viral-induced exacerbations in asthma.

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Section: Discussionmentioning

confidence: 95%

Rhinovirus-induced IFNβ expression is NFκB-dependent and regulated by the macrophage microenvironment

Menzel

Kosinski

Uller

et al. 2019

Sci Rep

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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).…”

mentioning

confidence: 99%

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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“…HPV detected in the rectal squamous cell carcinoma is associated with the increased macrophage M2 polarization 31 . In addition, the swine influenza virus 32 and rhinovirus 33 can also be involved in the regulation of macrophage conversion from M1 to M2 polarization. Saha et al 34 also found that hepatitis C virus can induce monocytes to differentiate into polarized M2 macrophages, which promotes the activation of stellate cells by TGF-β.…”

Section: Discussionmentioning

confidence: 99%

EB virus-induced ATR activation accelerates nasopharyngeal carcinoma growth via M2-type macrophages polarization

et al. 2020

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Chronic inflammation induced by persistent viruses infection plays an essential role in tumor progression, which influenced on the interaction between the tumor cells and the tumor microenvironment. Our earlier study showed that ATR, a key kinase participant in single-stranded DNA damage response (DDR), was obviously activated by Epstein–Barr virus (EBV) in nasopharyngeal carcinoma (NPC). However, how EBV-induced ATR activation promotes NPC by influencing inflammatory microenvironment, such as tumor-associated macrophages (TAMs), remains elusive. In this study, we showed that EBV could promote the expression of p-ATR and M2-type TAMs transformation in clinical NPC specimens. The expression of p-ATR and M2-type TAMs were closely correlated each other and involved in TNM stage, lymph node metastasis and poor prognosis of the patients. In addition, the expression levels of CD68+CD206+, Arg1, VEGF, and CCL22 were increased in EB+ CNE1 cells, and decreased when ATR was inhibited. In the nude mice, EBV-induced ATR activation promoted subcutaneous transplanted tumor growth, higher expression of Ki67 and lung metastasis via M2-type TAMs recruitment. Experimental data also showed that the polarization of M2, the declined tumor necrosis factor-α (TNF-α) and increased transforming growth factor-β (TGF-β) were associated with ATR. Meanwhile, ATR activation could promote PPAR-δ and inhibited c-Jun and p-JNK expression, then downregulate JNK pathway. Collectively, our current study demonstrated the EBV infection could activate the ATR pathway to accelerate the transition of TAMs to M2, suggesting ATR knockdown could be a potential effective treatment strategy for EBV-positive NPC.

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Rhinovirus infection induces distinct transcriptome profiles in polarized human macrophages

Cited by 18 publications

References 58 publications

Rhinovirus-induced IFNβ expression is NFκB-dependent and regulated by the macrophage microenvironment

Rhinovirus-induced IFNβ expression is NFκB-dependent and regulated by the macrophage microenvironment

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

EB virus-induced ATR activation accelerates nasopharyngeal carcinoma growth via M2-type macrophages polarization

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