Ontogeny of Toll-Like Receptor Mediated Cytokine Responses of Human Blood Mononuclear Cells
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{"title"=>"Ontogeny of toll-like receptor mediated cytokine responses of human blood mononuclear cells", "type"=>"journal", "authors"=>[{"first_name"=>"Nathan P.", "last_name"=>"Corbett", "scopus_author_id"=>"35745774200"}, {"first_name"=>"Darren", "last_name"=>"Blimkie", "scopus_author_id"=>"16041239000"}, {"first_name"=>"Kevin C.", "last_name"=>"Ho", "scopus_author_id"=>"36698834500"}, {"first_name"=>"Bing", "last_name"=>"Cai", "scopus_author_id"=>"7102841432"}, {"first_name"=>"Darren P.", "last_name"=>"Sutherland", "scopus_author_id"=>"16182817300"}, {"first_name"=>"Arlene", "last_name"=>"Kallos", "scopus_author_id"=>"6505978646"}, {"first_name"=>"Juliet", "last_name"=>"Crabtree", "scopus_author_id"=>"24365876000"}, {"first_name"=>"Annie", "last_name"=>"Rein-Weston", "scopus_author_id"=>"6504657408"}, {"first_name"=>"Pascal M.", "last_name"=>"Lavoie", "scopus_author_id"=>"7006151003"}, {"first_name"=>"Stuart E.", "last_name"=>"Turvey", "scopus_author_id"=>"12778474700"}, {"first_name"=>"Natalie R.", "last_name"=>"Hawkins", "scopus_author_id"=>"7102710456"}, {"first_name"=>"Steven G.", "last_name"=>"Self", "scopus_author_id"=>"34572681000"}, {"first_name"=>"Christopher B.", "last_name"=>"Wilson", "scopus_author_id"=>"56833137500"}, {"first_name"=>"Adeline M.", "last_name"=>"Hajjar", "scopus_author_id"=>"7003666839"}, {"first_name"=>"Edgardo S.", "last_name"=>"Fortuno", "scopus_author_id"=>"6508234206"}, {"first_name"=>"Tobias R.", "last_name"=>"Kollmann", "scopus_author_id"=>"6603926312"}], "year"=>2010, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"78649764135", "doi"=>"10.1371/journal.pone.0015041", "pui"=>"360095137", "pmid"=>"21152080", "scopus"=>"2-s2.0-78649764135", "issn"=>"19326203", "isbn"=>"1932-6203"}, "id"=>"b23a4a61-148b-34f3-a794-588f55577363", "abstract"=>"Newborns and young infants suffer increased infectious morbidity and mortality as compared to older children and adults. Morbidity and mortality due to infection are highest during the first weeks of life, decreasing over several years. Furthermore, most vaccines are not administered around birth, but over the first few years of life. A more complete understanding of the ontogeny of the immune system over the first years of life is thus urgently needed. Here, we applied the most comprehensive analysis focused on the innate immune response following TLR stimulation over the first 2 years of life in the largest such longitudinal cohort studied to-date (35 subjects). We found that innate TLR responses (i) known to support Th17 adaptive immune responses (IL-23, IL-6) peaked around birth and declined over the following 2 years only to increase again by adulthood; (ii) potentially supporting antiviral defense (IFN-α) reached adult level function by 1 year of age; (iii) known to support Th1 type immunity (IL-12p70, IFN-γ) slowly rose from a low at birth but remained far below adult responses even at 2 years of age; (iv) inducing IL-10 production steadily declined from a high around birth to adult levels by 1 or 2 years of age, and; (v) leading to production of TNF-α or IL-1β varied by stimuli. Our data contradict the notion of a linear progression from an 'immature' neonatal to a 'mature' adult pattern, but instead indicate the existence of qualitative and quantitative age-specific changes in innate immune reactivity in response to TLR stimulation.", "link"=>"http://www.mendeley.com/research/ontogeny-tolllike-receptor-mediated-cytokine-responses-human-blood-mononuclear-cells-6", "reader_count"=>67, "reader_count_by_academic_status"=>{"Unspecified"=>3, "Professor > Associate Professor"=>3, "Librarian"=>1, "Researcher"=>12, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>18, "Student > Postgraduate"=>4, "Student > Master"=>11, "Other"=>1, "Student > Bachelor"=>5, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>4}, "reader_count_by_user_role"=>{"Unspecified"=>3, "Professor > Associate Professor"=>3, "Librarian"=>1, "Researcher"=>12, "Student > Doctoral Student"=>3, "Student > Ph. D. Student"=>18, "Student > Postgraduate"=>4, "Student > Master"=>11, "Other"=>1, "Student > Bachelor"=>5, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>3, "Medicine and Dentistry"=>26, "Agricultural and Biological Sciences"=>28, "Neuroscience"=>1, "Social Sciences"=>1, "Immunology and Microbiology"=>5}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>26}, "Neuroscience"=>{"Neuroscience"=>1}, "Social Sciences"=>{"Social Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>5}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>28}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"Canada"=>2, "United States"=>1, "Spain"=>1, "Indonesia"=>1}, "group_count"=>5}

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  • {"files"=>["https://ndownloader.figshare.com/files/816054"], "description"=>"<p>Cytokines secreted by MC in tissue culture containing the indicated TLR ligands were measured by ELISA (IL-23) or by Luminex's xMAP cytokine assays. The MC were stimulated for 18 h at 37°C, 5% CO<sub>2</sub>, after which the supernatants were harvested and frozen at −80°C until time of assay. The IL-23 sandwich ELISA was done on samples from 25 neonate-infant subjects (0, 1, 2) and 25 adult subjects (A). The other cytokines were assayed via Luminex multiplex analysis for 35 neonate-infant subjects and 25 adult subjects. The y-axes represent the mean cytokine concentration in pg/ml; error bars indicate SEM. ND  =  not done.</p>", "links"=>[], "tags"=>["secreted", "cytokine", "tlr", "stimulation", "mc", "1-", "2-year"], "article_id"=>486389, "categories"=>["Developmental Biology", "Medicine", "Immunology"], "users"=>["Nathan P. Corbett", "Darren Blimkie", "Kevin C. Ho", "Bing Cai", "Darren P. Sutherland", "Arlene Kallos", "Juliet Crabtree", "Annie Rein-Weston", "Pascal M. Lavoie", "Stuart E. Turvey", "Natalie R. Hawkins", "Steven G. Self", "Christopher B. Wilson", "Adeline M. Hajjar", "Edgardo S. Fortuno III", "Tobias R. Kollmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0015041.g005", "stats"=>{"downloads"=>1, "page_views"=>10, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Bulk_measurement_of_secreted_cytokine_production_in_response_to_TLR_stimulation_of_MC_from_neonatal_1_and_2_year_olds_and_adult_/486389", "title"=>"Bulk measurement of secreted cytokine production in response to TLR stimulation of MC from neonatal, 1- and 2-year olds, and adult.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-11-30 01:46:29"}
  • {"files"=>["https://ndownloader.figshare.com/files/406671", "https://ndownloader.figshare.com/files/406704", "https://ndownloader.figshare.com/files/406731", "https://ndownloader.figshare.com/files/406762", "https://ndownloader.figshare.com/files/406772", "https://ndownloader.figshare.com/files/406790", "https://ndownloader.figshare.com/files/406798"], "description"=>"<div><p>Newborns and young infants suffer increased infectious morbidity and mortality as compared to older children and adults. Morbidity and mortality due to infection are highest during the first weeks of life, decreasing over several years. Furthermore, most vaccines are not administered around birth, but over the first few years of life. A more complete understanding of the ontogeny of the immune system over the first years of life is thus urgently needed. Here, we applied the most comprehensive analysis focused on the innate immune response following TLR stimulation over the first 2 years of life in the largest such longitudinal cohort studied to-date (35 subjects). We found that innate TLR responses (i) known to support Th17 adaptive immune responses (IL-23, IL-6) peaked around birth and declined over the following 2 years only to increase again by adulthood; (ii) potentially supporting antiviral defense (IFN-α) reached adult level function by 1 year of age; (iii) known to support Th1 type immunity (IL-12p70, IFN-γ) slowly rose from a low at birth but remained far below adult responses even at 2 years of age; (iv) inducing IL-10 production steadily declined from a high around birth to adult levels by 1 or 2 years of age, and; (v) leading to production of TNF-α or IL-1β varied by stimuli. Our data contradict the notion of a linear progression from an ‘immature’ neonatal to a ‘mature’ adult pattern, but instead indicate the existence of qualitative and quantitative age-specific changes in innate immune reactivity in response to TLR stimulation.</p> </div>", "links"=>[], "tags"=>["ontogeny", "toll-like", "receptor", "mediated", "cytokine", "responses", "mononuclear", "cells"], "article_id"=>140358, "categories"=>["Developmental Biology", "Medicine", "Immunology"], "users"=>["Nathan P. Corbett", "Darren Blimkie", "Kevin C. Ho", "Bing Cai", "Darren P. Sutherland", "Arlene Kallos", "Juliet Crabtree", "Annie Rein-Weston", "Pascal M. Lavoie", "Stuart E. Turvey", "Natalie R. Hawkins", "Steven G. Self", "Christopher B. Wilson", "Adeline M. Hajjar", "Edgardo S. Fortuno III", "Tobias R. Kollmann"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0015041.s001", "https://dx.doi.org/10.1371/journal.pone.0015041.s002", "https://dx.doi.org/10.1371/journal.pone.0015041.s003", "https://dx.doi.org/10.1371/journal.pone.0015041.s004", "https://dx.doi.org/10.1371/journal.pone.0015041.s005", "https://dx.doi.org/10.1371/journal.pone.0015041.s006", "https://dx.doi.org/10.1371/journal.pone.0015041.s007"], "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Ontogeny_of_Toll_Like_Receptor_Mediated_Cytokine_Responses_of_Human_Blood_Mononuclear_Cells/140358", "title"=>"Ontogeny of Toll-Like Receptor Mediated Cytokine Responses of Human Blood Mononuclear Cells", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2010-11-30 00:05:58"}
  • {"files"=>["https://ndownloader.figshare.com/files/815932"], "description"=>"<p>The MFI values from samples ran by the same operator and on the same machine for 10 subjects over the first two years of life (0, 1, and 2 years of age) were averaged after first excluding the samples that have cytokine-positive percentage <4% of the APC subtype. Means for each population are derived from the FloJo software; error bars indicate SEM.</p>", "links"=>[], "tags"=>["fluorescence", "intensities", "apc", "subpopulations", "produced", "cytokines", "tlr"], "article_id"=>486277, "categories"=>["Developmental Biology", "Medicine", "Immunology"], "users"=>["Nathan P. Corbett", "Darren Blimkie", "Kevin C. Ho", "Bing Cai", "Darren P. Sutherland", "Arlene Kallos", "Juliet Crabtree", "Annie Rein-Weston", "Pascal M. Lavoie", "Stuart E. Turvey", "Natalie R. Hawkins", "Steven G. Self", "Christopher B. Wilson", "Adeline M. Hajjar", "Edgardo S. Fortuno III", "Tobias R. Kollmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0015041.g004", "stats"=>{"downloads"=>3, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Mean_fluorescence_intensities_of_the_different_APC_subpopulations_that_produced_cytokines_in_response_to_TLR_stimulation_/486277", "title"=>"Mean fluorescence intensities of the different APC subpopulations that produced cytokines in response to TLR stimulation.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-11-30 01:44:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/815646"], "description"=>"<p>MC samples from 35 neonate-infant subjects (followed longitudinally as a cohort from birth (0), and then at 1-year (1) and 2-years (2) of life) and 25 adults (A) were stimulated with the indicated TLR ligands for 6 h, and the intracellular expression TNF-α, IL-6 and IL-12/23p40 by cDC was determined by multi-parameter flow cytometry. (A) Stacked bar graphs in which the overall height of the bar indicates the total percentage of cDC producing any cytokine (with statistically significant differences (p<0.01) between age groups indicated by *), and the height of each color indicates the percentage of cDC expressing an individual cytokine or cytokine combination (coded as shown in the inset, arranged from top to bottom in parallel the stacked bar). (B) The line graphs represent the qualitative summary of the polyfunctionality degree (PFD) for cDC after TLR stimulation of MC from samples isolated at the different age groups.</p>", "links"=>[], "tags"=>["tlr", "cdc", "intracellular", "cytokine"], "article_id"=>485989, "categories"=>["Developmental Biology", "Medicine", "Immunology"], "users"=>["Nathan P. Corbett", "Darren Blimkie", "Kevin C. Ho", "Bing Cai", "Darren P. Sutherland", "Arlene Kallos", "Juliet Crabtree", "Annie Rein-Weston", "Pascal M. Lavoie", "Stuart E. Turvey", "Natalie R. Hawkins", "Steven G. Self", "Christopher B. Wilson", "Adeline M. Hajjar", "Edgardo S. Fortuno III", "Tobias R. Kollmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0015041.g002", "stats"=>{"downloads"=>0, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Longitudinal_TLR_response_of_cDC_as_measured_by_intracellular_cytokine_staining_/485989", "title"=>"Longitudinal TLR response of cDC as measured by intracellular cytokine staining.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-11-30 01:39:49"}
  • {"files"=>["https://ndownloader.figshare.com/files/815539"], "description"=>"<p>MC samples from 35 neonate-infant subjects (followed longitudinally as a cohort from birth (0), and then at 1-year (1) and 2-years (2) of life) and 25 adults (A) were stimulated with the indicated TLR ligands for 6 h, and the intracellular expression TNF-α, IL-6 and IL-12/23p40 by monocytes was determined by multi-parameter flow cytometry. (A) Stacked bar graphs in which the overall height of the bar indicates the total percentage of monocytes producing any cytokine (with statistically significant differences (p<0.01) between age groups indicated by *), and the height of each color indicates the percentage of monocytes expressing an individual cytokine or cytokine combination (coded as shown in the inset, arranged from top to bottom in the same order as the stacked bar). (B) The line graphs represent the qualitative summary of the polyfunctionality degree (PFD) for monocytes after TLR stimulation of MC from samples isolated at the different age groups.</p>", "links"=>[], "tags"=>["tlr", "monocytes", "intracellular", "cytokine"], "article_id"=>485887, "categories"=>["Developmental Biology", "Medicine", "Immunology"], "users"=>["Nathan P. Corbett", "Darren Blimkie", "Kevin C. Ho", "Bing Cai", "Darren P. Sutherland", "Arlene Kallos", "Juliet Crabtree", "Annie Rein-Weston", "Pascal M. Lavoie", "Stuart E. Turvey", "Natalie R. Hawkins", "Steven G. Self", "Christopher B. Wilson", "Adeline M. Hajjar", "Edgardo S. Fortuno III", "Tobias R. Kollmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0015041.g001", "stats"=>{"downloads"=>1, "page_views"=>4, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Longitudinal_TLR_response_of_monocytes_as_measured_by_intracellular_cytokine_staining_/485887", "title"=>"Longitudinal TLR response of monocytes as measured by intracellular cytokine staining.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-11-30 01:38:07"}
  • {"files"=>["https://ndownloader.figshare.com/files/815763"], "description"=>"<p>MC samples from 35 neonate-infant subjects (followed longitudinally as a cohort from birth (0), and then at 1-year (1) and 2-years (2) of age) and 25 adults (A) were stimulated with the indicated TLR ligands for 6 h, and the intracellular expression TNF-α, IL-6 and IFN-α by pDC was determined by multi-parameter flow cytometry. (A) Stacked bar graphs in which the overall height of the bar indicates the total percentage of pDC producing any cytokine (with statistically significant differences (p<0.01) between age groups indicated by *), and the height of each color indicates the percentage of pDC expressing an individual cytokine or cytokine combination (coded as shown in the inset, arranged from top to bottom in parallel to the stacked bar). (B) The line graphs represent the qualitative summary of the polyfunctionality degree (PFD) for pDC after TLR stimulation of MC from samples isolated at the different age groups.</p>", "links"=>[], "tags"=>["tlr", "pdc", "intracellular", "cytokine"], "article_id"=>486111, "categories"=>["Developmental Biology", "Medicine", "Immunology"], "users"=>["Nathan P. Corbett", "Darren Blimkie", "Kevin C. Ho", "Bing Cai", "Darren P. Sutherland", "Arlene Kallos", "Juliet Crabtree", "Annie Rein-Weston", "Pascal M. Lavoie", "Stuart E. Turvey", "Natalie R. Hawkins", "Steven G. Self", "Christopher B. Wilson", "Adeline M. Hajjar", "Edgardo S. Fortuno III", "Tobias R. Kollmann"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0015041.g003", "stats"=>{"downloads"=>1, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Longitudinal_TLR_response_of_pDC_as_measured_by_intracellular_cytokine_staining_/486111", "title"=>"Longitudinal TLR response of pDC as measured by intracellular cytokine staining.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2010-11-30 01:41:51"}

PMC Usage Stats | Further Information

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