Influenza virus replication in macrophages: balancing protection and pathogenesis

Cline, Troy; Beck, Donald R.; Bianchini, Elizabeth

doi:10.1099/jgv.0.000922

Cited by 97 publications

(96 citation statements)

References 92 publications

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“…[276][277][278] In viral diseases, the macrophage response might be subverted to a certain extent by the numerous escape mechanisms that viral agents use to resist the host immune response. [279][280][281][282][283][284][285][286][287][288][289] Nevertheless, viruses generally trigger a response mediated by M1 macrophages that might contribute to the severity of the disease. In hepatitis C, chronic infection can lead to cell damage and cirrhosis, and the virus can induce an immune response, targeting the viral protein NS3, mediated by IL-12 and TNF-α produced by M1 macrophages.…”

Section: Autophagymentioning

confidence: 99%

<p>Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases</p>

Sousa¹,

Vasconcelos²,

Quaresma³

2019

IDR

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Macrophages are a functionally heterogeneous group of cells with specialized functions depending not only on their subgroup but also on the function of the organ or tissue in which the cells are located. The concept of macrophage phenotypic heterogeneity has been investigated since the 1980s, and more recent studies have identified a diverse spectrum of phenotypic subpopulations. Several types of macrophages play a central role in the response to infectious agents and, along with other components of the immune system, determine the clinical outcome of major infectious diseases. Here, we review the functions of various macrophage phenotypic subpopulations, the concept of macrophage polarization, and the influence of these cells on the evolution of infections. In addition, we emphasize their role in the immune response in vivo and in situ, as well as the molecular effectors and signaling mechanisms used by these cells. Furthermore, we highlight the mechanisms of immune evasion triggered by infectious agents to counter the actions of macrophages and their consequences. Our aim here is to provide an overview of the role of macrophages in the pathogenesis of critical transmissible diseases and discuss how elucidation of this relationship could enhance our understanding of the host–pathogen association in organ-specific immune responses.

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Section: Autophagymentioning

confidence: 99%

<p>Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases</p>

Sousa¹,

Vasconcelos²,

Quaresma³

2019

IDR

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“…Macrophages play a critical role in the regulation and induction of innate and adaptive immune responses and protection of the host against pathogens (15,62), especially viruses (19,20,37,38,63). However, recent findings demonstrated that macrophages could be a double-edged sword in virus clearance and pathology: they not only help fight against virus infection, but may also contribute to virus production and dissemination during viral infections (26,64). In mammal models, a number of viruses have been found target macrophages and impair the function of these cells (65)(66)(67).…”

Section: Discussionmentioning

confidence: 99%

“…The M1/M2 responses from virus infection must be balanced by inhibitory and regulatory effector mechanisms to protect bystander cell, tissue and organ damage from the effects of excess inflammation, preserve oxygenation, and promote host tissue and organ repair after viral clearance (22)(23)(24)(25). As their mammalian counterpart, plasticity also is a hallmark of chicken macrophages, and in response to microenvironment signals, including microbial infection and pathogenesis of infectious diseases (26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36), these cells undergo different forms of polarized activation, the extremes of which may called pro-inflammatory M1-like macrophages and anti-inflammatory M2-like macrophages.…”

mentioning

confidence: 99%

Enhanced Replication of Virulent Newcastle Disease Virus in Chicken Macrophages Is due to Polarized Activation of Cells by Inhibition of TLR7

et al. 2018

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Newcastle disease (ND), caused by infections with virulent strains of Newcastle disease virus (NDV), is one of the most important infectious disease affecting wild, peridomestic, and domestic birds worldwide. Vaccines constructed from live, low-virulence (lentogenic) viruses are the most accepted prevention and control strategies for combating ND in poultry across the globe. Avian macrophages are one of the first cell lines of defense against microbial infection, responding to signals in the microenvironment. Although macrophages are considered to be one of the main target cells for NDV infection in vivo, very little is known about the ability of NDV to infect chicken macrophages, and virulence mechanisms of NDV as well as the polarized activation patterns of macrophages and correlation with viral infection and replication. In the present study, a cell culture model (chicken bone marrow macrophage cell line HD11) and three different virulence and genotypes of NDV (including class II virulent NA-1, class II lentogenic LaSota, and class I lentogenic F55) were used to solve the above underlying questions. Our data indicated that all three NDV strains had similar replication rates during the early stages of infection. Virulent NDV titers were shown to increase compared to the other lentogenic strains, and this growth was associated with a strong upregulation of both pro-inflammatory M1-like markers/cytokines and anti-inflammatory M2-like markers/cytokines in chicken macrophages. Virulent NDV was found to block toll-like receptor (TLR) 7 expression, inducing higher expression of type I interferons in chicken macrophages at the late stage of viral infection. Only virulent NDV replication can be inhibited by pretreatment with TLR7 ligand. Overall, this study demonstrated that virulent NDV activates a M1-/M2-like mixed polarized activation of chicken macrophages by inhibition of TLR7, resulting in enhanced replication compared to lentogenic viruses.

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“…First, chemotactic signals important for the spatiotemporal distribution of immune cells are still largely unknown in ferrets; for example, influenza‐infected epithelial cells secrete CCL‐2 which recruits monocytes to the lungs during early infection and may be associated with acute lung injury during severe infections. Secondly, different innate immune subsets such as natural killer (NK) cells, dendritic cells (DCs), monocyte/macrophages and granulocytes have also yet to be studied in detail, and development of reagents to allow the delineation of these cell populations (reviewed in) will enable a more detailed picture of early immune responses in ferrets. Thirdly, while adaptive immune responses have been studied in ferrets, markers to delineate B/T‐cell subpopulations will be useful to study long‐term protection against influenza infection (as reviewed in).…”

Section: Ferrets As An Immunological Model For Studying Influenzamentioning

confidence: 99%

Improving immunological insights into the ferret model of human viral infectious disease

Wong

Layton

Wheatley

et al. 2019

Influenza Resp Viruses

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Influenza Other Respi Viruses. 2019;13:535-546. | 535 wileyonlinelibrary.com/journal/irv 1 | INTRODUC TI ON Animal models have proved critical in developing concepts of immunity to infection. Non-human primates (NHP) are a highly humanrelevant disease model for infectious agents due to high genetic conservation between humans and NHP. 1-3 However, significant cost and ethical issues often necessitate the use of smaller animal models for both basic and translational research. Mice (Mus musculus) are a favoured small animal model due to widespread availability, incisive transgenic models, comprehensive genomic information 4 and readily available reagents. However, for many viruses, alternative animal models better recapitulate human physiology and disease. Ferrets (Mustela putorius furo) have been employed to study the pathogenesis of a variety of human pathogens, including human and avian influenzas, coronaviruses including severe acute respiratory syndrome (SARS-CoV), 5-14 human respiratory syncytial virus (HRSV), 15-20 human metapneumovirus (HMPV), 21 Ebola virus 22-28 and henipavirus (Nipah virus and Hendra virus). 29-34 While ferretscan be productively infected with many of these viruses, a lack of some tools to interrogate ferret immunological responses to infection limits insights that might impact the development of vaccines and/or therapeutics. Here, we review recent insights gained from ferret models of human respiratory diseases, with a major focus on influenza, and highlight several knowledge gaps whose closure will greatly enhance the informational gain from ferret models to advance development of human vaccines and therapeutics. AbstractFerrets are a well-established model for studying both the pathogenesis and transmission of human respiratory viruses and evaluation of antiviral vaccines. Advanced immunological studies would add substantial value to the ferret models of disease but are hindered by the low number of ferret-reactive reagents available for flow cytometry and immunohistochemistry. Nevertheless, progress has been made to understand immune responses in the ferret model with a limited set of ferret-specific reagents and assays. This review examines current immunological insights gained from the ferret model across relevant human respiratory diseases, with a focus on influenza viruses. We highlight key knowledge gaps that need to be bridged to advance the utility of ferrets for immunological studies. K E Y W O R D S ferret, immunology, influenza How to cite this article: Wong J, Layton D, Wheatley AK, Kent SJ. Improving immunological insights into the ferret model of human viral infectious disease. Influenza Other Respi Viruses. 2019;13:535-546. https ://doi.

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Influenza virus replication in macrophages: balancing protection and pathogenesis

Cited by 97 publications

References 92 publications

<p>Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases</p>

<p>Functional aspects, phenotypic heterogeneity, and tissue immune response of macrophages in infectious diseases</p>

Enhanced Replication of Virulent Newcastle Disease Virus in Chicken Macrophages Is due to Polarized Activation of Cells by Inhibition of TLR7

Improving immunological insights into the ferret model of human viral infectious disease

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