Innate Immune Response of Human Alveolar Macrophages during Influenza A Infection
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{"title"=>"Innate immune response of human alveolar macrophages during influenza a infection", "type"=>"journal", "authors"=>[{"first_name"=>"Jieru", "last_name"=>"Wang", "scopus_author_id"=>"7701309561"}, {"first_name"=>"Mrinalini P.", "last_name"=>"Nikrad", "scopus_author_id"=>"26423983800"}, {"first_name"=>"Emily A.", "last_name"=>"Travanty", "scopus_author_id"=>"6507096634"}, {"first_name"=>"Bin", "last_name"=>"Zhou", "scopus_author_id"=>"55749740200"}, {"first_name"=>"Tzulip", "last_name"=>"Phang", "scopus_author_id"=>"55603014000"}, {"first_name"=>"Bifeng", "last_name"=>"Gao", "scopus_author_id"=>"7201753512"}, {"first_name"=>"Taylor", "last_name"=>"Alford", "scopus_author_id"=>"54398194900"}, {"first_name"=>"Yoko", "last_name"=>"Ito", "scopus_author_id"=>"55467331500"}, {"first_name"=>"Piruz", "last_name"=>"Nahreini", "scopus_author_id"=>"6701834271"}, {"first_name"=>"Kevan", "last_name"=>"Hartshorn", "scopus_author_id"=>"7007057790"}, {"first_name"=>"David", "last_name"=>"Wentworth", "scopus_author_id"=>"7004800841"}, {"first_name"=>"Charles A.", "last_name"=>"Dinarello", "scopus_author_id"=>"35390960400"}, {"first_name"=>"Robert J.", "last_name"=>"Mason", "scopus_author_id"=>"7403491658"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84863290608", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pui"=>"364370572", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0029879", "scopus"=>"2-s2.0-84863290608", "pmid"=>"22396727"}, "id"=>"5ba6efdc-ea98-38a7-a64d-083d7095a76d", "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.", "link"=>"http://www.mendeley.com/research/innate-immune-response-human-alveolar-macrophages-during-influenza-infection-4", "reader_count"=>84, "reader_count_by_academic_status"=>{"Unspecified"=>4, "Professor > Associate Professor"=>3, "Student > Doctoral Student"=>8, "Researcher"=>14, "Student > Ph. D. Student"=>29, "Student > Postgraduate"=>1, "Student > Master"=>11, "Other"=>2, "Student > Bachelor"=>10, "Professor"=>2}, "reader_count_by_user_role"=>{"Unspecified"=>4, "Professor > Associate Professor"=>3, "Student > Doctoral Student"=>8, "Researcher"=>14, "Student > Ph. D. 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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/673289"], "description"=>"<p>Human AM isolated from donor lungs were cultured and infected by PR/8 at a MOI of 0.5. Secretion of chemokines and cytokines from infected and non-infected cultures was measured by ELISA at 24 hpi. The data represent mean+SE of each released cytokine and chemokine (pg/ml). The number of individual donors ranged from 8 to 16. * indicates P<0.05, ** indicates P<0.01, *** indicates P<0.001 vs. non-infected cells.</p>", "links"=>[], "tags"=>["virus-induced", "secretion", "chemokines", "cytokines"], "article_id"=>343757, "categories"=>["Microbiology", "Virology", "Infectious Diseases", "Immunology", "Physiology", "Cell Biology"], "users"=>["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"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029879.g002", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Verification_of_virus_induced_secretion_of_chemokines_and_cytokines_by_ELISA_/343757", "title"=>"Verification of virus-induced secretion of chemokines and cytokines by ELISA.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-02 01:02:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/344053"], "description"=>"<div><p>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 <em>in vivo</em>.</p> </div>", "links"=>[], "tags"=>["innate", "alveolar", "macrophages", "influenza"], "article_id"=>127998, "categories"=>["Cancer", "Microbiology", "Immunology", "Physiology", "Cell Biology"], "users"=>["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"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029879", "stats"=>{"downloads"=>2, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Innate_Immune_Response_of_Human_Alveolar_Macrophages_during_Influenza_A_Infection/127998", "title"=>"Innate Immune Response of Human Alveolar Macrophages during Influenza A Infection", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-03-02 02:13:18"}
  • {"files"=>["https://ndownloader.figshare.com/files/673395"], "description"=>"<p>Primary AM were cultured and infected by live PR/8 at a MOI of 0.5 or the equal amount of UV-inactivated PR/8, and cells were harvested at designated time post inoculation. Panels A–F. Kinetics of viral antigen synthesis and infectious virus release. Panels A–C show representative immunofluorescence staining for influenza HA from live PR/8-infected AM culture at 6, 24, and 48 hpi. Panel D shows the quantitation of these experiments. The data represent mean±SE of percentage of positive-stained cells from 6 donors. Panel E. Representative staining of viral antigen in UV-inactivated PR/8 infection at 48 hpi. Panel F. Representative release of infectious viral particles from both live and UV-inactivated PR/8-infected AM from 6 donors. Panels G–K. Time course of cytokine and chemokine response in PR/8-infected AM. The supernatant from cultured cells were collected at 1, 6, 24, and 48 hpi. Secretion of TNF-α (Panel G), IFN-α (Panel H), CXCL10 (Panel I), CXCL8 (Panel J), and CCL5 (Panel K) was measured by ELISA. Data show representative release of each cytokine from infected AM of 6 donors that all showed similar response.</p>", "links"=>[], "tags"=>["influenza", "uv-inactivated"], "article_id"=>343866, "categories"=>["Microbiology", "Virology", "Infectious Diseases", "Immunology", "Physiology", "Cell Biology"], "users"=>["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"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029879.g003", "stats"=>{"downloads"=>1, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Kinetics_of_influenza_infection_with_live_and_UV_inactivated_PR_8_/343866", "title"=>"Kinetics of influenza infection with live and UV-inactivated PR/8.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-02 01:04:26"}
  • {"files"=>["https://ndownloader.figshare.com/files/673741"], "description"=>"<p>Human AM isolated from donor lungs were cultured and infected by PR/8 at a MOI of 0.5. Soluble TNF p55 receptor and IL-1Ra were added to the cultures at 10 µg/ml 45 min before the infection and added back to the cultures after viral inoculation. Secretion of chemokines and cytokines was measured by ELISA at 24 hpi. The data represent mean+SE of each released cytokine and chemokine (pg/ml). N = 6. * indicates P<0.05, ** indicates P<0.01, *** indicates P<0.001 vs. virus-infected cells.</p>", "links"=>[], "tags"=>["tnf", "il-1", "pathways", "decreases", "cxcl8", "ccl5", "cxcl10", "ifns", "induced", "influenza"], "article_id"=>344198, "categories"=>["Microbiology", "Virology", "Infectious Diseases", "Immunology", "Physiology", "Cell Biology"], "users"=>["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"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029879.g005", "stats"=>{"downloads"=>1, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Inhibition_of_TNF_and_or_IL_1_pathways_decreases_release_of_CXCL8_and_CCL5_but_not_CXCL10_and_IFNs_induced_by_influenza_infection_/344198", "title"=>"Inhibition of TNF and/or IL-1 pathways decreases release of CXCL8 and CCL5 but not CXCL10 and IFNs induced by influenza infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-02 01:09:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/673889"], "description"=>"<p>Panel A. Human AM were cultured and infected by PR/8 at a MOI of 0.5. The total RNA from infected and non-infected cells was evaluated for the expression of macrophage receptor genes by real-time RT-PCR at 24 hpi. The data show the relative expression levels of each gene in virus-infected cells compared to that of non-infected cells after normalized to the expression of constitutive probe from 4 to 14 donors. Each symbol indicates one donor. * indicates there was a significant difference between control and virus-infected cells (P<0.05). Panel B. PR/8 infection induced a dose-dependent decrease of uptake of zymosan. Isolated AM were cultured and infected by PR/8. At 24 hpi, fluorescent FITC-labeled zymosan was added without serum for 2 h and then the cells were washed and fixed with paraformaldehyde. Uptake of zymosan was measured as percent of cells containing zymosan evaluated under fluorescent microscopy. The data represent mean+SE of percent cells uptaking zymosan. N = 4. ** indicates P<0.01, *** indicates P<0.001 vs. non-infected cells.</p>", "links"=>[], "tags"=>["decreases", "clec7a", "mrna", "phagocytosis", "zymosan"], "article_id"=>344350, "categories"=>["Microbiology", "Virology", "Infectious Diseases", "Immunology", "Physiology", "Cell Biology"], "users"=>["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"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029879.g006", "stats"=>{"downloads"=>1, "page_views"=>12, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Influenza_virus_infection_decreases_CLEC7A_Dectin1_mRNA_and_reduces_phagocytosis_of_zymosan_by_AM_/344350", "title"=>"Influenza virus infection decreases CLEC7A (Dectin1) mRNA and reduces phagocytosis of zymosan by AM.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-02 01:12:30"}
  • {"files"=>["https://ndownloader.figshare.com/files/673550"], "description"=>"<p>Human AM isolated from donor lungs were cultured and infected by live NY/238 virus at a MOI of 0.1 or the equal amount of UV-inactivated NY/238. Cells were harvested at designated times for evaluation of their innate immune response. Panel A. Alterations in mRNAs of innate immune response-related genes at 3 and 24 hpi by realtime RT-PCR. The data represent mean+SE of the relative expression levels of each gene in infected cultures compared to that of non-infected controls after normalization to the level of the constitutive probe cyclophilin B, N = 4. * indicates P<0.05 and ** indicates P<0.01 between live and UV-inactivated cells. Panel B. Kinetics of cytokine and chemokine response by ELISA. The data show representative release of TNF-α, IFN-α, CXCL10, CXCL8, and CCL5 from both live and UV-inactivated NY/238 virus-infected AM from one of 6 donors that all showed similar response.</p>", "links"=>[], "tags"=>["uv-inactivated", "h3n2", "influenza", "viruses-infected"], "article_id"=>344015, "categories"=>["Microbiology", "Virology", "Infectious Diseases", "Immunology", "Physiology", "Cell Biology"], "users"=>["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"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029879.g004", "stats"=>{"downloads"=>1, "page_views"=>5, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Innate_immune_response_of_both_live_and_UV_inactivated_contemporary_H3N2_influenza_viruses_infected_AM_/344015", "title"=>"Innate immune response of both live and UV-inactivated contemporary H3N2 influenza viruses-infected AM.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-02 01:06:55"}
  • {"files"=>["https://ndownloader.figshare.com/files/674001"], "description"=>"<p>Human AM from 3 non-smoking donors were isolated, cultured, and infected by PR/8 virus at a MOI of 0.5. The gene profiling of infected and non-infected cells at 24 hpi from each donor was examined by microarray experiments using Affymetrix HG-U133 Plus 2.0 chips (Affymetrix, Santa Clara, CA). The filtered gene list was generated as described in the Section of <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029879#s4\" target=\"_blank\">Methods</a>. The data show the top 25 genes up-regulated or down-regulated altered by viral infection.</p><p>*indicates similar results from multiple probes.</p>", "links"=>[], "tags"=>["25", "genes", "up-regulated", "down-regulated", "am", "24"], "article_id"=>344464, "categories"=>["Microbiology", "Virology", "Infectious Diseases", "Immunology", "Physiology", "Cell Biology"], "users"=>["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"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029879.t002", "stats"=>{"downloads"=>1, "page_views"=>35, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_top_25_genes_up_regulated_or_down_regulated_by_PR_8_infection_in_human_AM_at_24_hpi_/344464", "title"=>"The top 25 genes up-regulated or down-regulated by PR/8 infection in human AM at 24 hpi.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-03-02 01:14:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/674060"], "description"=>"<p>Human AM from 3 non-smoking donors were isolated, cultured, and infected by PR/8 virus at a MOI of 0.5. The gene profiling of infected and non-infected cells at 4 hpi from each donor was examined by microarray experiments using Affymetrix HG-U133 Plus 2.0 chips (Affymetrix, Santa Clara, CA). The filtered gene list was generated as described in the Section of <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029879#s4\" target=\"_blank\">Methods</a>. The data show the top 25 genes up-regulated or down-regulated altered by viral infection.</p><p>*indicates similar results from multiple probes.</p>", "links"=>[], "tags"=>["25", "genes", "up-regulated", "down-regulated", "am"], "article_id"=>344523, "categories"=>["Microbiology", "Virology", "Infectious Diseases", "Immunology", "Physiology", "Cell Biology"], "users"=>["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"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029879.t001", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_top_25_genes_up_regulated_or_down_regulated_by_PR_8_infection_in_human_AM_at_4_hpi_/344523", "title"=>"The top 25 genes up-regulated or down-regulated by PR/8 infection in human AM at 4 hpi.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-03-02 01:15:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/673121"], "description"=>"<p>Human AM isolated from donor lungs were cultured and infected with PR/8 at a MOI of 0.5. Total RNA was isolated at 4 and 24 hpi from virus-infected and non-infected cultures. mRNA expression of IFN and IFN-associated genes were measured by real-time RT-PCR. The data represent mean+SE of the relative expression levels of each gene in infected cultures to that of non-infected controls after normalization to the level of the constitutive probe cyclophilin B, N = 8. Expression of all the tested genes are significantly different between virus-infected cultures and non-infected cultures, * indicates that the difference between 4 and 24 hpi is statistically significant (P<0.05).</p>", "links"=>[], "tags"=>["virus-induced", "mrnas", "ifn", "ifn-associated", "genes", "quantitative"], "article_id"=>343594, "categories"=>["Microbiology", "Virology", "Infectious Diseases", "Immunology", "Physiology", "Cell Biology"], "users"=>["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"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0029879.g001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Verification_of_virus_induced_increase_of_mRNAs_of_IFN_and_IFN_associated_genes_by_quantitative_RT_PCR_/343594", "title"=>"Verification of virus-induced increase of mRNAs of IFN and IFN-associated genes by quantitative RT-PCR.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-03-02 00:59:54"}

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