Cited by 122Influenza Virus Research StudiesSphingolipid Metabolism and SignalingImmunotoxicology and immune responses

A critical role for the sphingosine analog AAL-R in dampening the cytokine response during influenza virus infection

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Marsolais, David, Hahm, Bumsuk, Walsh, Kevin B., Edelmann, Kurt H., McGavern, Dorian, Hatta, Yasuko, Kawaoka, Yoshihiro, Rosen, Hugh +1 more·2009·Proceedings of the National Academy of Sciences

Abstract

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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Crossref · 10.1073/pnas.0812689106

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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
Venue
Proceedings of the National Academy of Sciences
Published
2009-02-03
Volume
106
Issue
5
Pages
1560-1565
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
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
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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