Secondary Bacterial Infections in Influenza Virus Infection Pathogenesis

Smith, Amber M.; McCullers, Jonathan A.

doi:10.1007/82_2014_394

Cited by 110 publications

(142 citation statements)

References 169 publications

(269 reference statements)

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“…the innate immune cell response, lung inflammatory response, and T cellular response, are also important to the defense against coinfection. Similar to the study of Wolf et al (20) and other reports (8,9,(39)(40)(41), the current study also demonstrated that coinfection significantly increased Ly6G ϩ neutrophils and F480 ϩ macrophages infiltrating the lung (Fig. 7A) and enhanced lung inflammatory cytokine and chemokine levels (Fig.…”

Section: Discussionsupporting

confidence: 91%

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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

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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

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Section: Discussionsupporting

confidence: 91%

“…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).…”

mentioning

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

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“…IAV infection is often made more severe by secondary bacterial infection of the upper respiratory tract [72]. While AM should serve as a protection against bacterial co-infection, bacterial clearance is impaired in a model of IAV/S.…”

Section: Iav Replication and Macrophage Phagocytosismentioning

confidence: 99%

Influenza virus replication in macrophages: balancing protection and pathogenesis

Cline

Beck

Bianchini

2017

Journal of General Virology

103

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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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“…17 We reasoned that the release of sTREM-1 is at least partly responsible for impaired innate immune responses to bacteria following influenza virus infection. We now report a matrix metalloproteinase (MMP)-9 cleavage site within the TREM-1 sequence and demonstrate an in vivo correlation between MMP-9 expression, the appearance of sTREM-1 in airway lavage and neutrophil recruitment during pulmonary influenza infection.…”

Section: Introductionmentioning

confidence: 99%

Reversal of TREM-1 ectodomain shedding and improved bacterial clearance by intranasal metalloproteinase inhibitors

et al. 2017

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Triggering receptor expressed on myeloid cells-1 (TREM-1) is expressed on neutrophils and monocyte/macrophages and amplifies Toll-like receptor-mediated inflammation during infection. TREM-1 also exists in an antagonistic soluble form (sTREM-1) that has been used as a peripheral biomarker in sepsis, though the mechanisms of its release are not entirely clear. The requirement of TREM-1 in single microbial infections is controversial, with some studies showing a protective role and others a contribution to immunopathology. Furthermore, the role of membrane-bound and sTREM-1 in polygenic infections is currently unknown. In a mouse co-infection model where preceding viral infection greatly enhances bacteria co-infection, we now determine a mechanisms for the striking increase in sTREM-1 and the loss of TREM-1 on surface of neutrophils. We identified a matrix metalloproteinase (MMP)-9 cleavage site in TREM-1 and that the increase of MMP-9 in bronchoalveolar lavage fluid mirrors sTREM-1 release. In vitro studies with neutrophils and MMP-9 and the reduction of sTREM-1 in vivo after MMP-9 inhibition verifies that this enzyme cleaves TREM-1. Intriguingly, MMP-9 inhibition significantly reduces bacterial load and ensuing immunopathology in a co-infection model. This highlights MMP-9 inhibition as a potential therapeutic via blocking cleavage of TREM-1.

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Secondary Bacterial Infections in Influenza Virus Infection Pathogenesis

Cited by 110 publications

References 169 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

Influenza virus replication in macrophages: balancing protection and pathogenesis

Reversal of TREM-1 ectodomain shedding and improved bacterial clearance by intranasal metalloproteinase inhibitors

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