Natural Killer Cells Are Involved in Acute Lung Immune Injury Caused by Respiratory Syncytial Virus Infection

Li, Fengqi; Zhu, Hongbo; Sun, Rui; Wei, Haiming; Tian, Zhigang

doi:10.1128/jvi.06209-11

Cited by 94 publications

(105 citation statements)

References 34 publications

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“…For instance, NK cells activated by poly I:C and D-galactosamine injection can cause overproduction of IFN-c, which causes damage to hepatocytes, 28 and NK cells are also involved in the lung immune injury at the early stage of respiratory syncytial virus infection. 29 Inspired by the findings in our study, we may control the extent of NK-cell activation using genetic methods to regulate the expression of activating and inhibitory receptors on NK cells, which may provide a therapy to improve the host's immune response or to control disease caused by excessive NK-cell immune response.…”

Section: Discussionmentioning

confidence: 92%

Lung natural killer cells in mice: phenotype and response to respiratory infection

Wang

Zheng

et al. 2012

Immunology

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SummaryNatural killer (NK) cells have a specialized function in peripheral organs, which is determined by the organ-specific niches. We have attempted to explore whether lung NK cells display a particular phenotype according to their function in the unique pulmonary environment in health or during respiratory infection in mice. In healthy mice, higher frequencies of NK cells among lymphocytes were detected in the lung than in other tissues (lymph node, bone marrow, spleen, blood and liver), and lung NK cells maintained a more mature phenotype, implying that lung NK cells were critical for the pulmonary immune response. However, lung NK cells expressed higher levels of inhibitory receptors and lower levels of activating receptors, migration/adhesion-associated molecules and co-stimulatory molecules than splenic NK cells, implying that lung NK cells were quiescent, and the activation of lung NK cells was tightly regulated by the pulmonary environment in health. During respiratory infection, lung NK cells could be activated and express functional molecules (CD107a and interferon-c) to take part in the response to infection quickly. These results suggested that the unique pulmonary environment promotes the development of NK cells with a lung-specific phenotype.

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Section: Discussionmentioning

confidence: 92%

Lung natural killer cells in mice: phenotype and response to respiratory infection

Wang

Zheng

et al. 2012

Immunology

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“…NK cells may participate in defense against respiratory pathogens via various mechanisms, including direct lysis of infected cells, production of chemokines that amplify the host's inflammatory response, production of antiviral cytokines, such as IFN-␥ and tumor necrosis factor alpha (TNF), and activation of DCs that mediate T cell differentiation and trafficking to the lung (23,26). In some instances, particularly during more severe respiratory infections, NK cells can be responsible for acute lung immune injury and mortality (27)(28)(29). While these studies suggest that NK activities can lead to both beneficial and deleterious outcomes, the role of NK cells and innate IFN-␥ and their relationship in early host defense against respiratory poxvirus infection have not been directly investigated.…”

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confidence: 99%

Natural Killer Cells and Innate Interferon Gamma Participate in the Host Defense against Respiratory Vaccinia Virus Infection

Abboud

Tahiliani

Desai

et al. 2016

J Virol

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In establishing a respiratory infection, vaccinia virus (VACV) initially replicates in airway epithelial cells before spreading to secondary sites of infection, mainly the draining lymph nodes, spleen, gastrointestinal tract, and reproductive organs. We recently reported that interferon gamma (IFN-␥) produced by CD8 T cells ultimately controls this disseminated infection, but the relative contribution of IFN-␥ early in infection is unknown. Investigating the role of innate immune cells, we found that the frequency of natural killer (NK) cells in the lung increased dramatically between days 1 and 4 postinfection with VACV. Lung NK cells displayed an activated cell surface phenotype and were the primary source of IFN-␥ prior to the arrival of CD8 T cells. In the presence of an intact CD8 T cell compartment, depletion of NK cells resulted in increased lung viral load at the time of peak disease severity but had no effect on eventual viral clearance, disease symptoms, or survival. In sharp contrast, RAG ؊/؊ mice devoid of T cells failed to control VACV and succumbed to infection despite a marked increase in NK cells in the lung. Supporting an innate immune role for NK cell-derived IFN-␥, we found that NK cell-depleted or IFN-␥-depleted RAG ؊/؊ mice displayed increased lung VACV titers and dissemination to ovaries and a significantly shorter mean time to death compared to untreated NK cell-competent RAG ؊/؊ controls. Together, these findings demonstrate a role for IFN-␥ in aspects of both the innate and adaptive immune response to VACV and highlight the importance of NK cells in T cell-independent control of VACV in the respiratory tract. IMPORTANCEHerein, we provide the first systematic evaluation of natural killer (NK) cell function in the lung after infection with vaccinia virus, a member of the Poxviridae family. The respiratory tract is an important mucosal site for entry of many human pathogens, including poxviruses, but precisely how our immune system defends the lung against these invaders remains unclear. Natural killer cells are a type of cytotoxic lymphocyte and part of our innate immune system. In recent years, NK cells have received increasing levels of attention following the discovery that different tissues contain specific subsets of NK cells with distinctive phenotypes and function. They are abundant in the lung, but their role in defense against respiratory viruses is poorly understood. What this study demonstrates is that NK cells are recruited, activated, and contribute to protection of the lung during a severe respiratory infection with vaccinia virus.

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“…Further study indicated that IL-17 promotes the secretion of cytokines inducing neutrophil migration, such as IL-1β, IL-6, and G-CSF, and further recruits neutrophils to the inflammation site in the lung (Huang et al, 2005;Tregoning et al, 2008;Li et al, 2012). This facilitates the removal of virus and an improvement in the survival rate.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-17 enhances the removal of respiratory syncytial virus in mice by promoting neutrophil migration and reducing interferon-gamma expression

Zhang

Zhou

2016

Genet. Mol. Res.

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ABSTRACT. The aim of this study was to observe the effect of interleukin (IL)-17 on early immune response and inflammation in the lungs of respiratory syncytial virus (RSV)-infected mice. Specific pathogen-free BALB/c mice were randomly assigned to control, RSV-infected, RSVinfected with phosphate-buffered saline, and RSV-infected + IL-17 intervention groups. The RSV infection model was set up by nasal mucosa immunization. The intervention group was provided with restructured IL-17 (intranasal). The viral load and cytokine concentrations in the lung tissues and broncho-alveolar lavage fluid (BALF) were determined by real-timepolymerase chain reaction and enzyme-linked immunosorbent assay.

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Natural Killer Cells Are Involved in Acute Lung Immune Injury Caused by Respiratory Syncytial Virus Infection

Abstract: It is known that respiratory syncytial virus (RSV) is

Cited by 94 publications

References 34 publications

Lung natural killer cells in mice: phenotype and response to respiratory infection

Lung natural killer cells in mice: phenotype and response to respiratory infection

Natural Killer Cells and Innate Interferon Gamma Participate in the Host Defense against Respiratory Vaccinia Virus Infection

Interleukin-17 enhances the removal of respiratory syncytial virus in mice by promoting neutrophil migration and reducing interferon-gamma expression

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