Innate immune response of human alveolar macrophages during influenza a infection

Jieru Wang, Mrinalini P. Nikrad, Emily A. Travanty, Bin Zhou, Tzulip Phang, Bifeng Gao, Taylor Alford, Yoko Ito, Piruz Nahreini, Kevan Hartshorn, David Wentworth, Charles A. Dinarello, Robert J. Mason

Research output: Contribution to journalArticle

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Abstract

Alveolar macrophages (AM) are one of the key cell types for initiating inflammatory and immune responses to influenza virus in the lung. However, the genome-wide changes in response to influenza infection in AM have not been defined. We performed gene profiling of human AM in response to H1N1 influenza A virus PR/8 using Affymetrix HG-U133 Plus 2.0 chips and verified the changes at both mRNA and protein levels by real-time RT-PCR and ELISA. We confirmed the response with a contemporary H3N2 influenza virus A/New York/238/2005 (NY/238). To understand the local cellular response, we also evaluated the impact of paracrine factors on virus-induced chemokine and cytokine secretion. In addition, we investigated the changes in the expression of macrophage receptors and uptake of pathogens after PR/8 infection. Although macrophages fail to release a large amount of infectious virus, we observed a robust induction of type I and type III interferons and several cytokines and chemokines following influenza infection. CXCL9, 10, and 11 were the most highly induced chemokines by influenza infection. UV-inactivation abolished virus-induced cytokine and chemokine response, with the exception of CXCL10. The contemporary influenza virus NY/238 infection of AM induced a similar response as PR/8. Inhibition of TNF and/or IL-1β activity significantly decreased the secretion of the proinflammatory chemokines CCL5 and CXCL8 by over 50%. PR/8 infection also significantly decreased mRNA levels of macrophage receptors including C-type lectin domain family 7 member A (CLEC7A), macrophage scavenger receptor 1 (MSR1), and CD36, and reduced uptake of zymosan. In conclusion, influenza infection induced an extensive proinflammatory response in human AM. Targeting local components of innate immune response might provide a strategy for controlling influenza A infection-induced proinflammatory response in vivo.

Original languageEnglish
Article numbere29879
JournalPLoS One
Volume7
Issue number3
DOIs
Publication statusPublished - 2012 Mar 2

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Alveolar Macrophages
Viruses
Innate Immunity
influenza
Human Influenza
macrophages
Chemokines
Infection
Macrophages
infection
chemokines
Orthomyxoviridae
Cytokines
cytokines
Genes
Influenza A virus
viruses
receptors
C-Type Lectins
Scavenger Receptors

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Wang, J., Nikrad, M. P., Travanty, E. A., Zhou, B., Phang, T., Gao, B., ... Mason, R. J. (2012). Innate immune response of human alveolar macrophages during influenza a infection. PLoS One, 7(3), [e29879]. https://doi.org/10.1371/journal.pone.0029879

Innate immune response of human alveolar macrophages during influenza a infection. / Wang, Jieru; Nikrad, Mrinalini P.; Travanty, Emily A.; Zhou, Bin; Phang, Tzulip; Gao, Bifeng; Alford, Taylor; Ito, Yoko; Nahreini, Piruz; Hartshorn, Kevan; Wentworth, David; Dinarello, Charles A.; Mason, Robert J.

In: PLoS One, Vol. 7, No. 3, e29879, 02.03.2012.

Research output: Contribution to journalArticle

Wang, J, Nikrad, MP, Travanty, EA, Zhou, B, Phang, T, Gao, B, Alford, T, Ito, Y, Nahreini, P, Hartshorn, K, Wentworth, D, Dinarello, CA & Mason, RJ 2012, 'Innate immune response of human alveolar macrophages during influenza a infection', PLoS One, vol. 7, no. 3, e29879. https://doi.org/10.1371/journal.pone.0029879
Wang J, Nikrad MP, Travanty EA, Zhou B, Phang T, Gao B et al. Innate immune response of human alveolar macrophages during influenza a infection. PLoS One. 2012 Mar 2;7(3). e29879. https://doi.org/10.1371/journal.pone.0029879
Wang, Jieru ; Nikrad, Mrinalini P. ; Travanty, Emily A. ; Zhou, Bin ; Phang, Tzulip ; Gao, Bifeng ; Alford, Taylor ; Ito, Yoko ; Nahreini, Piruz ; Hartshorn, Kevan ; Wentworth, David ; Dinarello, Charles A. ; Mason, Robert J. / Innate immune response of human alveolar macrophages during influenza a infection. In: PLoS One. 2012 ; Vol. 7, No. 3.
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