The aminobisphosphonate pamidronate controls influenza pathogenesis by expanding a γδ T cell population in humanized mice

Tu, Wenwei; Zheng, Jian; Liu, Yinping; Sia, Sin Fun; Liu, Ming; Qin, Gang; Ng, Iris H. Y.; Xiang, Zheng; Lam, Kwok-Tai; Peiris, Jsm; Lau, Yu‐Lung

doi:10.1084/jem.20110226

Cited by 108 publications

(151 citation statements)

References 68 publications

Supporting

Mentioning

147

Contrasting

Order By: Relevance

“…Mouse-adapted influenza virus A H1N1 (A/PR/8/34) (PR8) was cultured in Madin-Darby canine kidney cells as previously described by us (21,22). Virus titers were determined by observation of cytopathic effect in cells infected with serial dilutions of virus stock and further confirmed by hemagglutination assay; the median tissue culture infective dose (TCID 50 ) was calculated according to the Reed-Muench formula.…”

Section: Methodsmentioning

confidence: 99%

Lethal Coinfection of Influenza Virus and Streptococcus pneumoniae Lowers Antibody Response to Influenza Virus in Lung and Reduces Numbers of Germinal Center B Cells, T Follicular Helper Cells, and Plasma Cells in Mediastinal Lymph Node

Lam

et al. 2015

J Virol

Self Cite

View full text Add to dashboard Cite

Secondary Streptococcus pneumoniae infection after influenza is a significant clinical complication resulting in morbidity and sometimes mortality. Prior influenza virus infection has been demonstrated to impair the macrophage and neutrophil response to the subsequent pneumococcal infection. In contrast, how a secondary pneumococcal infection after influenza can affect the adaptive immune response to the initial influenza virus infection is less well understood. Therefore, this study focuses on how secondary pneumococcal infection after influenza may impact the humoral immune response to the initial influenza virus infection in a lethal coinfection mouse model. Compared to mice infected with influenza virus alone, mice coinfected with influenza virus followed by pneumococcus had significant body weight loss and 100% mortality. S econdary bacterial infection of the respiratory tract following influenza is a severe complication that often increases morbidity (1). Streptococcus pneumoniae is one of the pathogens that commonly cause the coinfection (2). Pneumococcus is also the major pathogen associated with mortality in both the 1918 Spanish influenza pandemic (3-5) and the 2009 H1N1 pandemic (6, 7). Given this clinical importance, it is imperative that we understand how the host immune response can be modulated after the coinfection.Prior influenza virus infection has been demonstrated to impair the immune defense against subsequent pneumococcal growth and infection (8, 9). For example, influenza virus can desensitize epithelial cells and alveolar macrophages to Toll-like receptor (TLR) signals for defense against bacteria (10). Gamma interferon (IFN-␥) induced by influenza virus can inhibit the phagocytosis of pneumococcus by macrophages (11). The type I IFN induced by influenza virus can impair neutrophils (12) and macrophages (13) in the defense against pneumococcus. Influenza virus can decrease tumor necrosis factor alpha (TNF-␣) production from natural killer cells in the lung, which allows an increase bacterial growth (14).In contrast, how secondary pneumococcal infection after influenza can influence the immune response to the initial influenza virus is relatively less well understood. The host adaptive immune response is largely responsible for controlling the influenza virus infection. It has been reported that coinfection could dysregulate Th17 (15) and gamma/delta T cells (16). However, whether the B cell response would be modulated during the coinfection is still not clear. It is reported that vaccine-induced immunity to influenza virus

show abstract

Section: Methodsmentioning

confidence: 99%

Lethal Coinfection of Influenza Virus and Streptococcus pneumoniae Lowers Antibody Response to Influenza Virus in Lung and Reduces Numbers of Germinal Center B Cells, T Follicular Helper Cells, and Plasma Cells in Mediastinal Lymph Node

Lam

et al. 2015

J Virol

Self Cite

View full text Add to dashboard Cite

show abstract

“…22,26,27 Moreover, these antiviral activities can be significantly improved by phosphoantigen stimulation, which confers sufficient protection on humanized mice to prevent lethal influenza virus infection. 28 In addition, another group has shown that cd-T cells can initiate efficient adaptive immunity through processing and presenting influenza virus-derived peptides to CD4 1 and CD8 1 T cells. 29 Moreover, cd-T cells have been found to promote the establishment of protective adaptive immunity against West Nile virus by inducing the maturation of dendritic cells (DCs).…”

Section: Involvement Of Cd-t Cells In Infectious Diseasesmentioning

confidence: 99%

“…Another impediment to studying the efficacy of phosphoantigen activation and expansion of Vc9Vd2 cd-T cells is the lack of an analogue in murine systems, which can be overcome by the development of a humanized mouse model. 28,137 Similarly, reliable animal models need to be established for evaluating the characteristics and clinical potential of human resident cd-T cells in mucosa and skin.…”

Section: Potential Of Cd-t Cell-based Therapy In Infectious Diseasesmentioning

confidence: 99%

See 1 more Smart Citation

γδ-T cells: an unpolished sword in human anti-infection immunity

et al. 2012

Self Cite

View full text Add to dashboard Cite

cd-T cells represent a small population of immune cells, but play an indispensable role in host defenses against exogenous pathogens, immune surveillance of endogenous pathogenesis and even homeostasis of the immune system. Activation and expansion of cd-T cells are generally observed in diverse human infectious diseases and correlate with their progression and prognosis. cd-T cells have both 'innate' and 'adaptive' characteristics in the immune response, and their anti-infection activities are mediated by multiple pathways that are under elaborate regulation by other immune components. In this review, we summarize the current state of the literature and the recent advancements in cd-T cell-mediated immune responses against common human infectious pathogens. Although further investigation is needed to improve our understanding of the characteristics of different cd-T cell subpopulations under specific conditions, cd-T cell-based therapy has great potential for the treatment of infectious diseases.

show abstract

“…15 Cytometric bead array analysis PBMCs or CBMCs were infected with influenza A virus at a multiplicity of infection (MOI) of 2 and cultured in RPMI-1640 media supplemented with 10% fetal bovine serum for 24 h. The culture supernatants were collected and cytokine (TNF-a and IFN-c) concentrations were measured using cytometric bead array (Becton & Dickinson, New Jersey, USA) as we described previously. 16 Data were acquired by flow cytometry and analysed with cytometric bead array software. Standard curves for each cytokine were generated to calculate their concentration in the tested samples.…”

Section: Cell Preparation and Influenza Virus Stimulationmentioning

confidence: 99%

Impaired NK cell antiviral cytokine response against influenza virus in small-for-gestational-age neonates

Mao

et al. 2013

Cell Mol Immunol

Self Cite

View full text Add to dashboard Cite

The neonates, particularly small-for-gestational-age (SGA) ones, are susceptible to various microbial infections. Natural killer (NK) cells are critical components of host innate immunity system and the main source of the inflammatory cytokines, which provide critical protection during the early phase of viral infections before the development of an appropriate adaptive immune response. However, little is known about the antiviral effects of NK cells in neonates especially the SGA population. Herein, a prospective descriptive study was performed to determine the differences of NK cell immunity among adults, appropriate-for gestational-age (AGA) and SGA neonates. Adults have much higher NK cell number in peripheral blood than that in cord blood from neonates. In response to influenza virus stimulation, neonatal NK cells, especially SGA baby cells, expressed significantly lower antiviral cytokines including perforin, interferon (IFN)-c and tumor-necrosis factor (TNF)-a responses than adult NK cells. In addition, the antiviral cytokine responses of NK cells were positively correlated with neonatal birth weight. Our data suggested that the depressed antiviral activity and less frequency of NK cells are likely to be responsible for the high susceptibility to microbial infection in neonates, at least in part. Improving the function of innate immunity may provide a new way to defend virus infection.

show abstract

The aminobisphosphonate pamidronate controls influenza pathogenesis by expanding a γδ T cell population in humanized mice

Abstract: As shown in humanized mice, a population of Vγ9Vδ2 T cells can reduce the severity and mortality of disease caused by infection with human and avian influenza viruses.

Cited by 108 publications

References 68 publications

Lethal Coinfection of Influenza Virus and Streptococcus pneumoniae Lowers Antibody Response to Influenza Virus in Lung and Reduces Numbers of Germinal Center B Cells, T Follicular Helper Cells, and Plasma Cells in Mediastinal Lymph Node

Lethal Coinfection of Influenza Virus and Streptococcus pneumoniae Lowers Antibody Response to Influenza Virus in Lung and Reduces Numbers of Germinal Center B Cells, T Follicular Helper Cells, and Plasma Cells in Mediastinal Lymph Node

γδ-T cells: an unpolished sword in human anti-infection immunity

Impaired NK cell antiviral cytokine response against influenza virus in small-for-gestational-age neonates

Contact Info

Product

Resources

About