Type I Interferon Induction during Influenza Virus Infection Increases Susceptibility to Secondary Streptococcus pneumoniae Infection by Negative Regulation of γδ T Cells

Li, Wenjing; Moltedo, Bruno; Moran, Thomas M.

doi:10.1128/jvi.01269-12

Cited by 176 publications

(195 citation statements)

References 48 publications

Supporting

Mentioning

182

Contrasting

Unclassified

Order By: Relevance

“…We detected prolonged and systemically increased levels of IL-6, which alone or together with type I IFNs induced by PR8 and S. pneumoniae (63,64) could account for the exaggerated ASC response in the medLN of PR8ϩSp-coinfected mice at day 10 p.i. This model is consistent with studies that demonstrated that IL-6, IFN-␥, and type I IFNs can enhance Ab responses (30,(65)(66)(67).…”

Section: Discussionmentioning

confidence: 81%

Coinfection with Streptococcus pneumoniae Modulates the B Cell Response to Influenza Virus

Wolf

Strauman

Mozdzanowska

et al. 2014

J Virol

View full text Add to dashboard Cite

Pathogen-specific antibodies (Abs) protect against respiratory infection with influenza A virus (IAV) and Streptococcus pneumoniae and are the basis of effective vaccines. Sequential or overlapping coinfections with both pathogens are common, yet the impact of coinfection on the generation and maintenance of Ab responses is largely unknown. We report here that the B cell response to IAV is altered in mice coinfected with IAV and S. pneumoniae and that this response differs, depending on the order of pathogen exposure. In mice exposed to S. pneumoniae prior to IAV, the initial virus-specific germinal center (GC) B cell response is significantly enhanced in the lung-draining mediastinal lymph node and spleen, and there is an increase in CD4 ؉ T follicular helper (TFH) cell numbers. In contrast, secondary S. pneumoniae infection exaggerates early antiviral antibody-secreting cell formation, and at later times, levels of GCs, TFH cells, and antiviral serum IgG are elevated. Mice exposed to S. pneumoniae prior to IAV do not maintain the initially robust GC response in secondary lymphoid organs and exhibit reduced antiviral serum IgG with diminished virus neutralization activity a month after infection. Our data suggest that the history of pathogen exposures can critically affect the generation of protective antiviral Abs and may partially explain the differential susceptibility to and disease outcomes from IAV infection in humans. IMPORTANCERespiratory tract coinfections, specifically those involving influenza A viruses and Streptococcus pneumoniae, remain a top global health burden. We sought to determine how S. pneumoniae coinfection modulates the B cell immune response to influenza virus since antibodies are key mediators of protection.

show abstract

Section: Discussionmentioning

confidence: 81%

Coinfection with Streptococcus pneumoniae Modulates the B Cell Response to Influenza Virus

Wolf

Strauman

Mozdzanowska

et al. 2014

J Virol

View full text Add to dashboard Cite

show abstract

“…Likewise, Wu et al (2015) showed the CD4 + T-cell population to be reduced during post-influenza pneumococcal infection. Moreover, influenza virus infection has been demonstrated to impair the release of IL-17 by TH17 cells and IL-17-producing gd T-cells during secondary infection of mice with bacteria (Kudva et al, 2011;Li et al, 2012). This aberrant production has been attributed to deficient IL-23 production by DCs (Kudva et al, 2011) and to suppressive effects of type I IFNs released during primary viral infection (Li et al, 2012).…”

Section: Alveolar Macrophages (Ams)mentioning

confidence: 99%

Viral–bacterial interactions in the respiratory tract

Bellinghausen

Rohde

Savelkoul

et al. 2016

Journal of General Virology

View full text Add to dashboard Cite

“…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.…”

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

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

Type I Interferon Induction during Influenza Virus Infection Increases Susceptibility to Secondary Streptococcus pneumoniae Infection by Negative Regulation of γδ T Cells

Cited by 176 publications

References 48 publications

Coinfection with Streptococcus pneumoniae Modulates the B Cell Response to Influenza Virus

Coinfection with Streptococcus pneumoniae Modulates the B Cell Response to Influenza Virus

Viral–bacterial interactions in the respiratory tract

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

Contact Info

Product

Resources

About