Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus.
Abstract
The 1918 influenza pandemic was unusually severe, resulting in about 50 million deaths worldwide. The 1918 virus is also highly pathogenic in mice, and studies have identified a multigenic origin of this virulent phenotype in mice. However, these initial characterizations of the 1918 virus did not address the question of its pathogenic potential in primates. Here we demonstrate that the 1918 virus caused a highly pathogenic respiratory infection in a cynomolgus macaque model that culminated in acute respiratory distress and a fatal outcome. Furthermore, infected animals mounted an immune response, characterized by dysregulation of the antiviral response, that was insufficient for protection, indicating that atypical host innate immune responses may contribute to lethality. The ability of influenza viruses to modulate host immune responses, such as that demonstrated for the avian H5N1 influenza viruses, may be a feature shared by the virulent influenza viruses.
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Where lymphopenia occurs, studies have shown a corresponding increase in macrophages, supported by increases in IP-10, IL-8, IL-6, and MCP-1.
“Where lymphopenia occurs, studies have shown a corresponding increase in macrophages.”
From Secondary bacterial infections associated with influenza pandemics (2017) · cites this paper as Kobasa et al., 2007
Strong upregulation of IL-6, IL-8, CCL2, and CCL5 cytokine and chemokine gene expression in the lungs was mirrored by elevated levels of IL-8, CCL2, and CCL5 in the sera of infected animals.
“For example, strong upregulation of IL-6, IL-8, CCL2, and CCL5 cytokine and chemokine gene expression in the lungs was mirrored by elevated levels of IL-8, CCL2, and CCL5 in the sera of infected animals (78).”
From Into the Eye of the Cytokine Storm (2012) · cites this paper as [78]
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- Authors
- Kobasa, D., Jones, S. M., Shinya, K., Kash, J. C., Copps, J., Ebihara, H., Hatta, Y., Hyun Kim, J., Halfmann, P., Hatta, M., Feldmann, F., Alimonti, J. B., Fernando, L., Li, Y., Katze, M. G., Feldmann, H., & Kawaoka, Y.
- Affiliations
- Public Health Agency of Canada (CA)
- Tottori University (JP)
- University of Washington (US)
- Canadian Food Inspection Agency (CA)
- University of Wisconsin–Madison (US)
- Corresponding author
- Kawaoka, Yoshihiro
- ORCID
- Venue
- Nature
- Published
- 2007-01-18
- Volume
- 445
- Issue
- 7125
- Pages
- 319-323
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2073234751
- Cited by
- 934
- References
- 31
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 6 · 2023: 22 · 2022: 36 · 2021: 46 · 2020: 40 · 2019: 40 · 2018: 36 · 2017: 51 · 2016: 37 · 2015: 32 · 2014: 49 · 2013: 66 · 2012: 62
- FWCI
- 68.09
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Public Health Agency of Canada
- Public Health Agency
- Japan Society for the Promotion of Science (CREST)
- Japan Science and Technology Agency (CREST)
- Core Research for Evolutional Science and Technology
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Keywords
- Spanish flu pandemic, innate immune suppression, cynomolgus macaque model, H5N1 avian influenza, respiratory distress
- MeSH terms
- Animals, Disease Models, Animal, Female, Gene Expression Regulation, Humans, Immunity, Innate, Influenza, Human, Lung, Macaca fascicularis, Mice, Inbred BALB C, Time Factors, Virus Replication, Survival Rate, Cytokines, Chemokines, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Mice, Influenza A Virus, H1N1 Subtype
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