Bacterial colonization dampens influenza-mediated acute lung injury via induction of M2 alveolar macrophages

Wang, Jian; Li, Fengqi; Sun, Rui; Gao, Xiang; Wei, Haiming; Li, Lan Juan; Tian, Zhigang

doi:10.1038/ncomms3106

Cited by 190 publications

(181 citation statements)

References 46 publications

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“…Whilst these studies were carried out with BMDMs rather than alveolar macrophages, they provide important clues for understanding the function of macrophages in control of influenza virus infections. Wang et al (2013) recently showed that alternatively activated alveolar macrophages can protect against lethal challenge in a mouse model. Their study did not address macrophage infection, but our data would suggest that infection of alternatively activated macrophages per se is likely to play a role in this protective effect.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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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“…In our previous work, we chose Staphylococcus aureus, a common commensal bacterium in the upper respiratory tract, to build a mouse model of bacterial preinfection and found that it dampened the subsequent influenza-induced "cytokine storm" through a mechanism involving the induction of the immuneinhibitory M2 macrophage cells (16). In this S. aureus preinfection model, the most optimal protective effect occurred when mice were infected with S. aureus 3 d before PR8 infection; if mice were infected with S. aureus 7 d before PR8 infection, the protective effect was weakened.…”

Section: Discussionmentioning

confidence: 99%

“…Measurement of total protein, cytokines, and Igs in bronchoalveolar lavage fluid or serum Bronchoalveolar lavage fluid (BALF) was collected as previously described (16). In brief, the lungs were washed once with 1 ml sterile saline through an intratracheal cannula.…”

Section: Mouse Infectionsmentioning

confidence: 99%

Klebsiella pneumoniaeAlleviates Influenza-Induced Acute Lung Injury via Limiting NK Cell Expansion

Wang

Sun

et al. 2014

The Journal of Immunology

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A protective effect induced by bacterial preinfection upon a subsequent lethal influenza virus infection has been observed, but the underlying immune mechanisms have not yet been fully elucidated. In this study, we used a mouse model of Klebsiella pneumoniae preinfection to gain insight into how bacterial preinfection influences the subsequent lethal influenza virus infection. We found that K. pneumoniae preinfection significantly attenuated lung immune injury and decreased mortality during influenza virus infection, but K. pneumoniae–specific immunity was not involved in this cross-protection against influenza virus. K. pneumoniae preinfection limited NK cell expansion, which was involved in influenza-induced immune injury and death. Furthermore, K. pneumoniae preinfection could not control NK cell expansion and death during influenza virus infection in Rag1−/− mice, but adoptive transfer of T cells from wild-type mice was able to restore this protective effect. Our data suggest that the adaptive immune response activated by bacterial infection limits the excessive innate immune response induced by a subsequent influenza infection, ultimately protecting mice from death.

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“…Treatment of mice with this bacterium before influenza inoculation reduced lung damage during influenza infection. Mechanistically, this protection was due to the recruitment of monocytes from the blood, which subsequently differentiated into anti‐inflammatory M2 alveolar macrophages in the lung 65. These macrophages inhibit the recruitment of excessive inflammatory cells during infection and it is thought that this reduces tissue damage and mortality caused by influenza.…”

Section: Host Resistance To Airway Infection and The Microbiotamentioning

confidence: 99%

The regulation of host defences to infection by the microbiota

Brown

Clarke

2016

Immunology

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SummaryThe skin and mucosal epithelia of humans and other mammals are permanently colonized by large microbial communities (the microbiota). Due to this life‐long association with the microbiota, these microbes have an extensive influence over the physiology of their host organism. It is now becoming apparent that nearly all tissues and organ systems, whether in direct contact with the microbiota or in deeper host sites, are under microbial influence. The immune system is perhaps the most profoundly affected, with the microbiota programming both its innate and adaptive arms. The regulation of immunity by the microbiota helps to protect the host against intestinal and extra‐intestinal infection by many classes of pathogen. In this review, we will discuss the experimental evidence supporting a role for the microbiota in regulating host defences to extra‐intestinal infection, draw together common mechanistic themes, including the central role of pattern recognition receptors, and outline outstanding questions that need to be answered.

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Bacterial colonization dampens influenza-mediated acute lung injury via induction of M2 alveolar macrophages

Cited by 190 publications

References 46 publications

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

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

Klebsiella pneumoniaeAlleviates Influenza-Induced Acute Lung Injury via Limiting NK Cell Expansion

The regulation of host defences to infection by the microbiota

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