PI3K/Akt Signaling Pathway Modulates Influenza Virus Induced Mouse Alveolar Macrophage Polarization to M1/M2b

Zhao, Xiaohong; Dai, Jianping; Xiao, Xuejun; Wu, Liqi; Zeng, Jun; Sheng, Jiangtao; Su, Jinghua; Chen, Xiaoxuan; Wang, Gefei; Li, Kangsheng

doi:10.1371/journal.pone.0104506

Cited by 47 publications

(43 citation statements)

References 55 publications

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“…The cells were analyzed using fluorescence-activated cell sorting (FACS). The BAL cells were seeded on plates for 2 h and non-adherent cells were washed, and the adherent cells were scraped and fixed with 4% paraformaldehyde at 4 °C for 30 min, and then incubated for 2 h with a 1:100 dilution of the CD11b/c antibody and F4/80 antibody (Ebioscience, San Diego, United States) labeled with Alexa Fluor 488 for flow cytometry analysis[19]. …”

Section: Methodsmentioning

confidence: 99%

IRF5 regulates lung macrophages M2 polarization during severe acute pancreatitisin vitro

Sun¹,

He²,

Qu³

et al. 2016

WJG

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AIMTo investigate the role of interferon regulatory factor 5 (IRF5) in reversing polarization of lung macrophages during severe acute pancreatitis (SAP) in vitro.METHODSA mouse SAP model was established by intraperitoneal (ip) injections of 20 μg/kg body weight caerulein. Pathological changes in the lung were observed by hematoxylin and eosin staining. Lung macrophages were isolated from bronchoalveolar lavage fluid. The quantity and purity of lung macrophages were detected by fluorescence-activated cell sorting and evaluated by real-time polymerase chain reaction (RT-PCR). They were treated with IL-4/IRF5 specific siRNA (IRF5 siRNA) to reverse their polarization and were evaluated by detecting markers expression of M1/M2 using RT-PCR.RESULTSSAP associated acute lung injury (ALI) was induced successfully by ip injections of caerulein, which was confirmed by histopathology. Lung macrophages expressed high levels of IRF5 as M1 phenotype during the early acute pancreatitis stages. Reduction of IRF5 expression by IRF5 siRNA reversed the action of macrophages from M1 to M2 phenotype in vitro. The expressions of M1 markers, including IRF5 (S + IRF5 siRNA vs S + PBS, 0.013 ± 0.01 vs 0.054 ± 0.047, P < 0.01), TNF-α (S + IRF5 siRNA vs S + PBS, 0.0003 ± 0.0002 vs 0.019 ± 0.018, P < 0.001), iNOS (S + IRF5 siRNA vs S + PBS, 0.0003 ± 0.0002 vs 0.026 ± 0.018, P < 0.001) and IL-12 (S + IRF5 siRNA vs S + PBS, 0.000005 ± 0.00004 vs 0.024 ± 0.016, P < 0.001), were decreased. In contrast, the expressions of M2 markers, including IL-10 (S + IRF5 siRNA vs S + PBS, 0.060 ± 0.055 vs 0.0230 ± 0.018, P < 0.01) and Arg-1 (S + IRF5 siRNA vs S + PBS, 0.910 ± 0.788 vs 0.0036 ± 0.0025, P < 0.001), were increased. IRF5 siRNA could reverse the lung macrophage polarization more effectively than IL-4.CONCLUSIONTreatment with IRF5 siRNA can reverse the pancreatitis-induced activation of lung macrophages from M1 phenotype to M2 phenotype in SAP associated with ALI.

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Section: Methodsmentioning

confidence: 99%

IRF5 regulates lung macrophages M2 polarization during severe acute pancreatitisin vitro

Sun¹,

He²,

Qu³

et al. 2016

WJG

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“…A PI3K inhibitor decreased expression of CD16 on microglial cells (central nervous system-resident macrophages), suggesting a link between PI3K signalling and Fc receptor expression [69]. Although seasonal H1N1 and H3N2 IAV activate the PI3K signalling pathway in mouse AMs, an H5N1 IAV fails to do the same in infected epithelial cells [70,71]. While the status of PI3K signalling in H5-infected macrophages has not been investigated, perhaps a failure to activate the PI3K pathway in macrophages is one explanation for the observed decrease in CD16/32 expression that leads to the decreased phagocytic capacity of H5-infected macrophages.…”

Section: Iav Replication and Macrophage Phagocytosismentioning

confidence: 99%

Influenza virus replication in macrophages: balancing protection and pathogenesis

Cline

Beck

Bianchini

2017

Journal of General Virology

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Macrophages are essential for protection against influenza A virus infection, but are also implicated in the morbidity and mortality associated with severe influenza disease, particularly during infection with highly pathogenic avian influenza (HPAI) H5N1 virus. While influenza virus infection of macrophages was once thought to be abortive, it is now clear that certain virus strains can replicate productively in macrophages. This may have important consequences for the antiviral functions of macrophages, the course of disease and the outcome of infection for the host. In this article, we review findings related to influenza virus replication in macrophages and the impact of productive replication on macrophage antiviral functions. A clear understanding of the interactions between influenza viruses and macrophages may lead to new antiviral therapies to relieve the burden of severe disease associated with influenza viruses.

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“…In addition, viral reassortment and cross-infection play a contributory role in the ineffectiveness of the vaccine. In particular, previous studies have provided evidence that the severity of viral infection is associated with some environmental, nutritional, and immune factors, such as mycotoxin contamination [3,4], selenium deficiency [5,6], and macrophage polarization [7]. These factors may partially explain the global differences in morbidity and mortality in animals and humans.…”

Section: Introductionmentioning

confidence: 99%

Low-Level Aflatoxin B1 Promotes Influenza Infection and Modulates a Switch in Macrophage Polarization from M1 to M2

Sun

Liu

et al. 2018

Cell Physiol Biochem

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Background/Aims: Swine influenza virus (SIV) is a major pathogen of both animals and humans. Afatoxin B1 (AFB₁) is one of the most common mycotoxins in feed and food. However, the central contribution of AFB₁ to SIV infection remains unclear. Methods: Here, TCID₅₀ assays, fluorescence-based quantitative real-time PCR, western blotting, immunofluorescence staining, histopathological examination, flow cytometry and scanning electron microscopy were performed to investigate the involvement and underlying mechanism of AFB₁ in SIV infection in vivo and in vitro using mouse models and porcine alveolar macrophage (PAM) models, respectively. Results: The in vivo study showed that low levels of AFB₁ promoted SIV infection and increased its severity, as demonstrated by the increased mRNA expression of viral matrix protein (M); by the increased protein expression of nucleoprotein (NP), matrix protein 1 and ion channel protein; and by animal weight loss, lung index and lung histologic damage. In addition, the increased occurrence of SIV infection accompanied by increases in the level of IL-10 in sera and lungs, in the spleen index and in the number of CD206-positive mouse alveolar macrophages but decreases in the level of TNF-α in sera and lungs, in the thymus index and in the number of CD80-positive mouse alveolar macrophages was observed in SIV-infected mice after low-level AFB₁ exposure. The in vitro study showed that low concentrations of AFB₁ promoted SIV infection, as demonstrated by the increases in viral titers and viral M mRNA and NP expression levels in SIV-infected PAMs as well as by the number of cells positive for NP protein expression. Furthermore, AFB₁ promoted the polarization of SIV-infected PAMs to the M1 phenotype at 8 hpi and to the M2 phenotype at 24 hpi, as measured by the increases in IL-10 expression and in the number of CD206-positive PAMs as well as by the morphological changes observed by scanning electron microscopy. The administration of the immune stimulant lipopolysaccharide (LPS) reversed the switch in PAM polarization from M2 to M1 and thereby counteracted the promotion of influenza virus infection induced by AFB₁. Conclusion: Our results are the first to confirm that low-level exposure to AFB₁ promotes SIV infection and modulates a switch in macrophage polarization from M1 to M2. The work reported here provides important data that point to a role for AFB₁ in SIV infection, and it opens a new field of study.

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PI3K/Akt Signaling Pathway Modulates Influenza Virus Induced Mouse Alveolar Macrophage Polarization to M1/M2b

Cited by 47 publications

References 55 publications

IRF5 regulates lung macrophages M2 polarization during severe acute pancreatitisin vitro

IRF5 regulates lung macrophages M2 polarization during severe acute pancreatitisin vitro

Influenza virus replication in macrophages: balancing protection and pathogenesis

Low-Level Aflatoxin B1 Promotes Influenza Infection and Modulates a Switch in Macrophage Polarization from M1 to M2

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