Pathogenicity of Influenza Viruses with Genes from the 1918 Pandemic Virus: Functional Roles of Alveolar Macrophages and Neutrophils in Limiting Virus Replication and Mortality in Mice

Tumpey, Terrence M.; Garcı́a-Sastre, Adolfo; Taubenberger, Jeffery K.; Palese, Peter; Swayne, David E.; Pantin‐Jackwood, Mary J.; Schultz‐Cherry, Stacey; Solórzano, Alicia; Rooijen, Nico van; Katz, Jacqueline M.; Basler, Christopher F.

doi:10.1128/jvi.79.23.14933-14944.2005

Cited by 473 publications

(514 citation statements)

References 76 publications

Supporting

Mentioning

475

Contrasting

Unclassified

Order By: Relevance

“…A more substantial mobilization of neutrophils in lungs of mice was also observed at 1 h after LTB 4 administration (data not shown). The number of neutrophils in lungs of mice infected with influenza virus was also found to increase, a process that may reflect a natural host defense against virus infection, as previously suggested by others (45). In line with these results, a massive neutrophil recruitment was also observed in lung tissues of mice infected with influenza virus and treated with LTB 4 as opposed to all other experimental groups of mice (Table II).…”

Section: Neutrophils Contribute To the Antiviral Activity Of Ltb 4 Insupporting

confidence: 79%

Leukotriene B4 Induces Release of Antimicrobial Peptides in Lungs of Virally Infected Mice

Gaudreault

Gosselin

2008

The Journal of Immunology

View full text Add to dashboard Cite

Leukotriene B4 (LTB4) is a lipid mediator of inflammation that was recently shown to exert antiviral activities. In this study, we demonstrate that the release of antimicrobial proteins by neutrophils contribute to an early host defense against influenza virus infection in vitro as well as in vivo. Daily i.v. treatments with LTB4 lead to a significant decrease in lung viral loads at day 5 postinfection in mice infected with influenza A virus compared with the placebo-treated group. This reduction in viral load was not present in mice deficient in the high-affinity LTB4 receptor. Viral clearance in lungs was associated with up-regulated presence of antimicrobial peptides such as β-defensin-3, members of the mouse eosinophil-related RNase family, and the mouse cathelicidin-related antimicrobial peptide. Our results also indicate that neutrophils are important in the antiviral effect of LTB4. Viral loads in neutrophil-depleted mice were not diminished by LTB4 administration, and a substantial reduction in the presence of murine cathelicidin-related antimicrobial peptide and the murine eosinophil-related RNase family in lung tissue was observed. Moreover, in vitro treatment of human neutrophil cultures with LTB4 led rapidly to the secretion of the human cathelicidin LL-37 and eosinophil-derived neurotoxin, known as antiviral peptides. Pretreatment of cell cultures with specific LTB4 receptor antagonists clearly demonstrate the implication of the high-affinity LTB4 receptor in the LTB4-mediated activity. Together, these results demonstrate the importance of neutrophils and the secretion of antimicrobial peptides during the early immune response mediated by LTB4 against a viral pathogen.

show abstract

Section: Neutrophils Contribute To the Antiviral Activity Of Ltb 4 Insupporting

confidence: 79%

Leukotriene B4 Induces Release of Antimicrobial Peptides in Lungs of Virally Infected Mice

Gaudreault

Gosselin

2008

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…While the mouse serves as a convenient model to study factors that may modulate disease severity, previous attempts to elucidate the role of neutrophils have been limited by reliance on the use of mAb RB6-8C5 to deplete Ly6G high neutrophils in vivo (2,7,9,26). Herein, we demonstrate that mAb 1A8 can be used to identify and deplete Ly6G high neutrophils from mice during influenza virus infection.…”

Section: Discussionmentioning

confidence: 93%

“…Neutrophils are a characteristic and prominent feature of the early inflammatory response to influenza virus infection of humans, ferrets, and mice (1), but their role in host defense remains unclear. Recent studies using the reconstructed virulent 1918 Spanish influenza pandemic virus (H1N1) or highly pathogenic H5N1 viruses to infect mice showed that neutrophils (and macrophages) predominate in the airways early after infection (2,3). Therapeutic blockade of the neutrophil-attracting chemokine MIP-2 was associated with reduced neutrophil recruitment and a milder lung pathology following infection with mouse-adapted A/PR/8/34 virus (PR8, H1N1), suggesting that dysregulated or excessive neutrophil responses might contribute to disease during severe influenza infection (4).…”

mentioning

confidence: 99%

“…RB6-85C has been used extensively to deplete Ly6G ϩ neutrophils in murine models of infection and inflammation (reviewed in Ref. 8), including influenza infection (2,7,9). While Ly6G is the major Ag detected by mAb RB6-8C5 (10), it is clear that this mAb also binds to the Ly6C Ag expressed by additional leukocyte populations, including subsets of monocytes, dendritic cells (DC), 3 and CD8 ϩ T cells (11), implicated in anti-viral host defense, confounding interpretation of cellular mechanisms.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Neutrophils Ameliorate Lung Injury and the Development of Severe Disease during Influenza Infection

Tate

Deng

Jones

et al. 2009

The Journal of Immunology

283

308

View full text Add to dashboard Cite

The clinical response to influenza infection ranges from mild disease to severe pneumonia and it remains unclear whether the inflammatory response to infection is protective or pathogenic. We have defined a novel role for neutrophils in ameliorating lung injury during influenza infection, thereby limiting development of severe disease. Infection of neutrophil-depleted mice with influenza virus HKx31 (H3N2) led to rapid weight loss, pneumonia, and death. Neutropenia was associated with enhanced virus replication in the respiratory tract; however, viral titers were declining at the time of death, leading us to investigate other factors contributing to mortality. In addition to thymic atrophy, lymphopenia, and viremic spread, depletion of neutrophils led to exacerbated pulmonary inflammation, edema, and respiratory dysfunction. Thus, while it is well established that neutrophils contribute to lung injury in a range of pathological conditions, reduced numbers or impaired neutrophil function can facilitate progression of mild influenza to severe clinical disease.

show abstract

“…People exposed to H1N1 viruses in the late 1940s had detectable antibodies against H1N1 in the 1978 outbreak 38 . Also, some people naturally infected with the 1918 H1N1 virus between 1928 and 1933 still have antibody titres against the 1918 viruses 39 . Therefore, a vaccine inducing cross‐reactivity would be of great value in preventing influenza.…”

Section: Discussionmentioning

confidence: 99%

Pandemic influenza 1918 H1N1 and 1968 H3N2 DNA vaccines induce cross-reactive immunity in ferrets against infection with viruses drifted for decades

Bragstad

Martel

Thomsen

et al. 2010

Influenza and Other Respiratory Viruses

View full text Add to dashboard Cite

Please cite this paper as: Bragstad et al. (2010) Pandemic influenza 1918 H1N1 and 1968 H3N2 DNA vaccines induce cross‐reactive immunity in ferrets against infection with viruses drifted for decades. Influenza and Other Respiratory Viruses 5(1), 13–23. Background Alternative influenza vaccines and vaccine production forms are needed as the conventional protein vaccines do not induce broad cross‐reactivity against drifted strains. Furthermore, fast vaccine production is especially important in a pandemic situation, and broader vaccine reactivity would diminish the need for frequent change in the vaccine formulations. Objective In this study, we compared the ability of pandemic influenza DNA vaccines to induce immunity against distantly related strains within a subtype with the immunity induced by conventional trivalent protein vaccines against homologous virus challenge. Methods Ferrets were immunised by particle‐mediated epidermal delivery (gene gun) with DNA vaccines based on the haemagglutinin (HA) and neuraminidase (NA) and/or the matrix (M) and nucleoprotein genes of the 1918 H1N1 Spanish influenza pandemic virus or the 1968 H3N2 Hong Kong influenza pandemic virus. The animals were challenged with contemporary H1N1 or H3N2 viruses. Results We demonstrated that DNA vaccines encoding proteins of the original 1918 H1N1 pandemic virus induced protective cross‐reactive immune responses in ferrets against infection with a 1947 H1N1 virus and a recent 1999 H1N1 virus. Similarly, a DNA vaccine, based on the HA and NA of the 1968 H3N2 pandemic virus, induced cross‐reactive immune responses against a recent 2005 H3N2 virus challenge. Conclusions DNA vaccines based on pandemic or recent seasonal influenza genes induced cross‐reactive immunity against contemporary virus challenge as good as or superior to contemporary conventional trivalent protein vaccines. This suggests a unique ability of influenza DNA to induce cross‐protective immunity against both contemporary and long‐time drifted viruses.

show abstract

Pathogenicity of Influenza Viruses with Genes from the 1918 Pandemic Virus: Functional Roles of Alveolar Macrophages and Neutrophils in Limiting Virus Replication and Mortality in Mice

Cited by 473 publications

References 76 publications

Leukotriene B4 Induces Release of Antimicrobial Peptides in Lungs of Virally Infected Mice

Leukotriene B4 Induces Release of Antimicrobial Peptides in Lungs of Virally Infected Mice

Neutrophils Ameliorate Lung Injury and the Development of Severe Disease during Influenza Infection

Pandemic influenza 1918 H1N1 and 1968 H3N2 DNA vaccines induce cross-reactive immunity in ferrets against infection with viruses drifted for decades

Contact Info

Product

Resources

About