Responses of Mouse Airway Epithelial Cells and Alveolar Macrophages to Virulent and Avirulent Strains of Influenza A Virus

Tate, Michelle D.; Schilter, Heidi; Brööks, Andrëw G.; Reading, Patrick C.

doi:10.1089/vim.2010.0118

Cited by 70 publications

(99 citation statements)

References 62 publications

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“…When the virus was inactivated by UV irradiation, PR8-induced cytokine expression in human AMs was shown to be replication-dependent [29]. Consistent with other studies on PR8 [11,27,28,32], this study reported very little, if any, productive release of PR8 into macrophage culture supernatants, even in the absence of UV inactivation. However, virus antigen in cells infected with live virus increased over the first 48 h post-infection, a response that was abrogated by UV inactivation of the virus.…”

Section: Iav Replication and Hypercytokinemiasupporting

confidence: 89%

“…In this case, virus nucleoprotein (NP) accumulated in 20 % of infected cells, but virus release was undetected [26]. Other studies support the findings of early experiments [11,[27][28][29]. However, certain seasonal H1N1 and H3N2 strains are capable of limited productive replication in mouse bone marrow-derived macrophages (BMDMs) or human MDMs, respectively [30][31][32][33].…”

Section: Replication Of Iav In Macrophagesmentioning

confidence: 55%

“…This was accompanied by a corresponding decrease in the transcription of CLEC7A, a receptor for fungal cell wall glucans [29]. PR8 infection is abortive in RAW264.7, PEC macrophages and BAL macrophages [11,28,32], and was, at best, shown to be only moderately productive in human AMs by Wang et al Thus, it is unlikely that the decreased phagocytic capacity and CLEC7A expression following IAV infection are due to productive virus replication. A direct comparison of the effects on macrophage phagocytosis of live and UV-inactivated PR8 infection is necessary to conclude what role virus replication plays in decreasing phagocytic capacity.…”

Section: Iav Replication and Macrophage Phagocytosismentioning

confidence: 98%

“…In contrast, mouse PEC macrophages and bronchoalveolar lavage (BAL) macrophages that predominantly express a2,6-linked sialic acid receptors show poor susceptibility to infection with a PR8 IAV strain that binds preferentially to a2,3-linked sialic acids [11,28,41]. Variability in the receptor-binding preference of PR8 viruses of different origins has been reported, with the PR8 Warwick strain binding equally well to a2,3-linked and a2,6-linked receptors [42].…”

Section: Mechanism Of Iav Restriction In Macrophagesmentioning

confidence: 99%

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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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Section: Iav Replication and Hypercytokinemiasupporting

confidence: 89%

Section: Replication Of Iav In Macrophagesmentioning

confidence: 55%

Section: Iav Replication and Macrophage Phagocytosismentioning

confidence: 98%

Section: Mechanism Of Iav Restriction In Macrophagesmentioning

confidence: 99%

See 2 more Smart Citations

Influenza virus replication in macrophages: balancing protection and pathogenesis

Cline

Beck

Bianchini

2017

Journal of General Virology

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“…It is notable, however, that the apparently more permissive state of alternatively activated macrophages did not lead to production of higher levels of infectious virus than are found in classically activated cells. Although there is evidence for productive influenza virus infections in human macrophages (Hoeve et al, 2012;Perrone et al, 2008;van Riel et al, 2011;Yu et al, 2011), a number of publications have reported that influenza virus infection is abortive in murine macrophages (Rodgers & Mims, 1981;Tate et al, 2010Tate et al, , 2011. Our data show that whilst there is some replication of A/WSN/33 in murine BMDMs, the ability to produce infectious virus is not related to the activation state of the macrophage.…”

Section: Discussioncontrasting

confidence: 48%

Susceptibility of bone marrow-derived macrophages to influenza virus infection is dependent on macrophage phenotype

Campbell

Nicol

Dransfield

et al. 2015

Journal of General Virology

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The role of the macrophage in influenza virus infection is complex. Macrophages are critical for resolution of influenza virus infections but implicated in morbidity and mortality in severe infections. They can be infected with influenza virus and consequently macrophage infection is likely to have an impact on the host immune response. Macrophages display a range of functional phenotypes, from the prototypical pro-inflammatory classically activated cell to alternatively activated anti-inflammatory macrophages involved in immune regulation and wound healing. We were interested in how macrophages of different phenotype respond to influenza virus infection and therefore studied the infection of bone marrow-derived macrophages (BMDMs) of classical and alternative phenotype in vitro. Our results show that alternatively activated macrophages are more readily infected and killed by the virus than classically activated. Classically activated BMDMs express the pro-inflammatory markers inducible nitric oxide synthase (iNOS) and TNF-a, and TNF-a expression was further upregulated following infection. Alternatively activated macrophages express Arginase-1 and CD206; however, following infection, expression of these markers was downregulated whilst expression of iNOS and TNF-a was upregulated. Thus, infection can override the anti-inflammatory state of alternatively activated macrophages. Importantly, however, this results in lower levels of proinflammatory markers than those produced by classically activated cells. Our results showed that macrophage phenotype affects the inflammatory macrophage response following infection, and indicated that modulating the macrophage phenotype may provide a route to develop novel strategies to prevent and treat influenza virus infection.

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Naturally derived cytokine peptides limit virus replication and severe disease during influenza A virus infection

et al. 2023

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Objectives. Novel host-targeted therapeutics could treat severe influenza A virus (IAV) infections, with reduced risk of drug resistance. LAT8881 is a synthetic form of the naturally occurring C-terminal fragment of human growth hormone. Acting independently of the growth hormone receptor, it can reduce inflammation-induced damage and promote tissue repair in an animal model of osteoarthritis. LAT8881 has been assessed in clinical trials for the treatment of obesity and neuropathy and has an excellent safety profile. We investigated the potential for LAT8881, its metabolite LAT9991F and LAT7771 derived from prolactin, a growth hormone structural homologue, to treat severe IAV infection. Methods. LAT8881, LAT9991F and LAT7771 were evaluated for their effects on cell viability and IAV replication in vitro, as well as their potential to limit disease in a preclinical mouse model of severe IAV infection. Results. In vitro LAT8881 treatment enhanced cell viability, particularly in the presence of cytotoxic stress, which was countered by siRNA inhibition of host lanthionine synthetase C-like proteins. Daily intranasal treatment of mice with LAT8881 or LAT9991F, but not LAT7771, from day 1 postinfection significantly improved influenza disease resistance, which was associated with reduced infectious viral loads, reduced pro-inflammatory cytokines and increased abundance of protective alveolar macrophages. LAT8881 treatment in combination with the antiviral oseltamivir phosphate led to more pronounced reduction in markers of disease severity than treatment with either compound alone. Conclusion. These studies provide the first evidence identifying LAT8881 and LAT9991F as novel host-protective therapies that improve survival, limit viral replication, reduce local inflammation and curtail tissue damage during severe IAV infection. Evaluation of LAT8881 and LAT9991F in other infectious and inflammatory conditions of the airways is warranted.

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Responses of Mouse Airway Epithelial Cells and Alveolar Macrophages to Virulent and Avirulent Strains of Influenza A Virus

Cited by 70 publications

References 62 publications

Influenza virus replication in macrophages: balancing protection and pathogenesis

Influenza virus replication in macrophages: balancing protection and pathogenesis

Susceptibility of bone marrow-derived macrophages to influenza virus infection is dependent on macrophage phenotype

Naturally derived cytokine peptides limit virus replication and severe disease during influenza A virus infection

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