Title |
Innate Immune Response of Human Alveolar Macrophages during Influenza A Infection
|
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Published in |
PLOS ONE, March 2012
|
DOI | 10.1371/journal.pone.0029879 |
Pubmed ID | |
Authors |
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 |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Australia | 1 | 33% |
United States | 1 | 33% |
Unknown | 1 | 33% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 67% |
Scientists | 1 | 33% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 3 | 2% |
United Kingdom | 2 | 1% |
Germany | 1 | <1% |
Brazil | 1 | <1% |
Belgium | 1 | <1% |
Canada | 1 | <1% |
Unknown | 173 | 95% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 39 | 21% |
Researcher | 35 | 19% |
Student > Master | 26 | 14% |
Student > Bachelor | 22 | 12% |
Student > Doctoral Student | 13 | 7% |
Other | 21 | 12% |
Unknown | 26 | 14% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 59 | 32% |
Immunology and Microbiology | 36 | 20% |
Medicine and Dentistry | 24 | 13% |
Biochemistry, Genetics and Molecular Biology | 15 | 8% |
Pharmacology, Toxicology and Pharmaceutical Science | 4 | 2% |
Other | 12 | 7% |
Unknown | 32 | 18% |