A critical role for the sphingosine analog AAL-R in dampening the cytokine response during influenza virus infection
Open accessAbstract
Pulmonary tissue damage resulting from influenza virus infection is caused by both the cytolytic activity of the virus and the host immune response. Immune-mediated injury results from T cell-mediated destruction of virus-infected cells and by release of cytokines and chemokines that attract polymorphonuclear leukocytes (PML) and macrophages to the infected site. The cytokines/chemokines potentiate dendritic cell (DC) activation and T cell expansion, which further enhances local damage. Here we report that immune modulation by local administration to the respiratory tract of sphingosine analog AAL-R significantly dampens the release of cytokines and chemokines while maintaining protective neutralizing antibody and cytotoxic T cell responses. As a result there was a marked reduction of infiltrating PML and macrophages into the lung and resultant pulmonary tissue injury. DC maturation was suppressed, which limited proliferation of specific antiviral T cells in the lung and draining lymph nodes. Further, AAL-R was effective in controlling CD8 + T cell accumulation in the lungs even when given 4 days after initiation of influenza virus infection. These data indicate that sphingosine analogs display useful potential for controlling the immunopathology caused by influenza virus.
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Sphingosine analogs have shown potential for controlling the cytokine storm caused by influenza virus.
“and sphingosine analogs have shown potential for controlling the cytokine storm caused by influenza virus (95).”
From Into the Eye of the Cytokine Storm (2012) · cites this paper as [95]
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- Authors
- Marsolais, D., Hahm, B., Walsh, K. B., Edelmann, K. H., McGavern, D., Hatta, Y., Kawaoka, Y., Rosen, H., & Oldstone, M. B. A.
- Affiliations
- Scripps Research Institute (US)
- University of Wisconsin–Madison (US)
- Corresponding author
- Rosen, Hugh
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-02-03
- Volume
- 106
- Issue
- 5
- Pages
- 1560-1565
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2635800
- OpenAlex
- W2030510738
- Cited by
- 122
- References
- 35
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 1 · 2022: 4 · 2021: 3 · 2020: 7 · 2019: 3 · 2018: 3 · 2017: 8 · 2016: 11 · 2015: 9 · 2014: 19 · 2013: 14 · 2012: 7
- FWCI
- 8.51
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Public Health Service (NIMH-074404)
- National Institute of Allergy and Infectious Diseases (AI-074564, R01AI070967, AI069274, R01AI009484, R01AI069274, AI-009484, U01AI074564, AI05509, R56AI069274)
- Topics
- Health Sciences › Medicine › Epidemiology › Influenza Virus Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
- Keywords
- influenza, cytokine response, chemokines, pulmonary immunopathology, dendritic cell maturation, CD8+ T cells, polymorphonuclear leukocytes, macrophages, T cell-mediated injury, immunomodulation, neutralizing antibodies
- MeSH terms
- Amino Acid Sequence, Animals, Antibodies, Viral, Antigen-Presenting Cells, Base Sequence, Disease Models, Animal, DNA, Viral, Humans, Influenza, Human, Lung, Molecular Sequence Data, Neutralization Tests, Sphingosine, T-Lymphocytes, Cytotoxic, Cytokines, Mice
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