Reduced T Regulatory Cell Response during Acute Plasmodium falciparum Infection in Malian Children Co-Infected with Schistosoma haematobium
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{"title"=>"Reduced T regulatory cell response during acute plasmodium falciparum infection in malian children co-infected with schistosoma haematobium", "type"=>"journal", "authors"=>[{"first_name"=>"Kirsten E.", "last_name"=>"Lyke", "scopus_author_id"=>"6603189919"}, {"first_name"=>"Abdoulaye", "last_name"=>"Dabo", "scopus_author_id"=>"6603619434"}, {"first_name"=>"Charles", "last_name"=>"Arama", "scopus_author_id"=>"14822047000"}, {"first_name"=>"Modibo", "last_name"=>"Daou", "scopus_author_id"=>"10739895300"}, {"first_name"=>"Issa", "last_name"=>"Diarra", "scopus_author_id"=>"8532364900"}, {"first_name"=>"Amy", "last_name"=>"Wang", "scopus_author_id"=>"54975472700"}, {"first_name"=>"Christopher V.", "last_name"=>"Plowe", "scopus_author_id"=>"7004231133"}, {"first_name"=>"Ogobara K.", "last_name"=>"Doumbo", "scopus_author_id"=>"7005026392"}, {"first_name"=>"Marcelo B.", "last_name"=>"Sztein", "scopus_author_id"=>"7005394979"}], "year"=>2012, "source"=>"PLoS ONE", "identifiers"=>{"issn"=>"19326203", "pui"=>"364261122", "doi"=>"10.1371/journal.pone.0031647", "sgr"=>"84856873108", "scopus"=>"2-s2.0-84856873108", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pmid"=>"22348117"}, "id"=>"7eeba6bc-f43a-38b3-b1f5-c6789c3d5fcb", "abstract"=>"BACKGROUND: Regulatory T cells (Tregs) suppress host immune responses and participate in immune homeostasis. In co-infection, secondary parasite infections may disrupt the immunologic responses induced by a pre-existing parasitic infection. We previously demonstrated that schistosomiasis-positive (SP) Malian children, aged 4-8 years, are protected against the acquisition of malaria compared to matched schistosomiasis-negative (SN) children.\\n\\nMETHODS AND FINDINGS: To determine if Tregs contribute to this protection, we performed immunologic and Treg depletion in vitro studies using PBMC acquired from children with and without S. haematobium infection followed longitudinally for the acquisition of malaria. Levels of Tregs were lower in children with dual infections compared to children with malaria alone (0.49 versus 1.37%, respectively, P = 0.004) but were similar months later, during a period with negligible malaria transmission. The increased levels of Tregs in SN subjects were associated with suppressed serum Th1 cytokine levels, as well as elevated parasitemia compared to co-infected counterparts.\\n\\nCONCLUSIONS: These results suggest that lower levels of Tregs in helminth-infected children correlate with altered circulating cytokine and parasitologic results which may play a partial role in mediating protection against falciparum malaria.", "link"=>"http://www.mendeley.com/research/reduced-t-regulatory-cell-response-during-acute-plasmodium-falciparum-infection-malian-children-coin", "reader_count"=>31, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>10, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>3, "Student > Postgraduate"=>1, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>2, "Researcher"=>10, "Student > Doctoral Student"=>5, "Student > Ph. D. Student"=>3, "Student > Postgraduate"=>1, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>2, "Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>4, "Mathematics"=>1, "Agricultural and Biological Sciences"=>9, "Medicine and Dentistry"=>6, "Immunology and Microbiology"=>6}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>6}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>6}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>9}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Mathematics"=>{"Mathematics"=>1}, "Unspecified"=>{"Unspecified"=>3}}, "reader_count_by_country"=>{"Netherlands"=>1, "Burkina Faso"=>1, "United States"=>1}, "group_count"=>1}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/348612", "https://ndownloader.figshare.com/files/348648"], "description"=>"<div><h3>Background</h3><p>Regulatory T cells (Tregs) suppress host immune responses and participate in immune homeostasis. In co-infection, secondary parasite infections may disrupt the immunologic responses induced by a pre-existing parasitic infection. We previously demonstrated that schistosomiasis-positive (SP) Malian children, aged 4–8 years, are protected against the acquisition of malaria compared to matched schistosomiasis-negative (SN) children.</p> <h3>Methods and Findings</h3><p>To determine if Tregs contribute to this protection, we performed immunologic and Treg depletion <em>in vitro</em> studies using PBMC acquired from children with and without <em>S. haematobium</em> infection followed longitudinally for the acquisition of malaria. Levels of Tregs were lower in children with dual infections compared to children with malaria alone (0.49 versus 1.37%, respectively, P = 0.004) but were similar months later, during a period with negligible malaria transmission. The increased levels of Tregs in SN subjects were associated with suppressed serum Th1 cytokine levels, as well as elevated parasitemia compared to co-infected counterparts.</p> <h3>Conclusions</h3><p>These results suggest that lower levels of Tregs in helminth-infected children correlate with altered circulating cytokine and parasitologic results which may play a partial role in mediating protection against falciparum malaria.</p> </div>", "links"=>[], "tags"=>["reduced", "acute", "malian", "children", "co-infected"], "article_id"=>128926, "categories"=>["Immunology", "Cancer", "Physiology"], "users"=>["Kirsten E. Lyke", "Abdoulaye Dabo", "Charles Arama", "Modibo Daou", "Issa Diarra", "Amy Wang", "Christopher V. Plowe", "Ogobara K. Doumbo", "Marcelo B. Sztein"], "doi"=>[nil, nil], "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Reduced_T_Regulatory_Cell_Response_during_Acute_em_Plasmodium_falciparum_em_Infection_in_Malian_Children_Co_Infected_with_em_Schistosoma_haematobium_em_/128926", "title"=>"Reduced T Regulatory Cell Response during Acute <em>Plasmodium falciparum</em> Infection in Malian Children Co-Infected with <em>Schistosoma haematobium</em>", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2012-02-14 02:28:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/683345"], "description"=>"<p><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031647#s3\" target=\"_blank\">Results</a> of enhanced cytokine expression to antigenic stimulation after CD25<sup>hi</sup> depletion of PBMC followed by antigenic stimulation in comparison to mock-depleted populations. The numerator represents the number of children with enhanced Interleukin 2 (IL-2) or Interferon-gamma (IFN-γ) expression after depletion compared to mock-depletion. The denominator is the number of children examined. The net percentage of cytokine expressed in CD3<sup>+</sup>CD4<sup>+</sup>CD8<sup>−</sup> T cells (i.e., depletion results minus mock-depletion results) after depletion as measured by multiparameter flow cytometry is also depicted in those experiments with significant cytokine expression increase. Cells were acquired from age-matched children aged 4–14 years with or without <i>S. haematobium</i> during the malaria transmission (wet) season and again during a dry season follow-up visit. Also depicted are results from SP children who did not acquire malaria (SP no Mal) during the wet season.</p>a<p>Stratification between younger children aged 4–8 years and older children aged 9–14 years revealed no significant difference so results are reported as a combined age cohort of children aged 4–14 years.</p>b<p>PBMC were stimulated with a <i>P. falciparum</i> antigen pool (Apical Membrane antigen 1 and Merozoite Surface Protein 1) or with a <i>S. haematobium</i> antigen pool (soluble egg antigen and soluble worm antigen protein).</p>c<p>The mean percentage increase represents the average of the net increase in cytokine production (stimulant wells minus media wells) of those experiments with statistically significant results. Significance is defined by 1) net percentage of cytokine producing cells ≥0.05% in CD25hi-depleted compared to mock-depleted PBMC, 2) the number of positive events between depleted and mock-depleted cultures was significant by Chi-square analysis and 3) the number of positive events in the stimulant pool compared to the media control in depleted cultures was significantly increased.</p>", "links"=>[], "tags"=>["depletion", "assay"], "article_id"=>353833, "categories"=>["Physiology", "Infectious Diseases", "Immunology"], "users"=>["Kirsten E. Lyke", "Abdoulaye Dabo", "Charles Arama", "Modibo Daou", "Issa Diarra", "Amy Wang", "Christopher V. Plowe", "Ogobara K. Doumbo", "Marcelo B. Sztein"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031647.t003", "stats"=>{"downloads"=>0, "page_views"=>2, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_CD25_hi_Depletion_Assay_Results_/353833", "title"=>"CD25<sup>hi</sup> Depletion Assay Results.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-02-14 01:03:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/683426"], "description"=>"<p>Demographic characteristics at enrollment and features of subsequent <i>P. falciparum</i> malaria infections of <i>Schistosoma haematobium</i>-positive (SP Mal) and age-matched <i>S. haematobium</i>-negative (SN Mal) Malian children contributing PBMC for immunologic analysis.<sup><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031647#nt102\" target=\"_blank\">a</a></sup></p>a<p>Urinary egg excretion detected in 10 ml of filtered morning (10 am to 2 pm) urine.</p>b<p><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031647#s3\" target=\"_blank\">Results</a> for children who did not develop malaria (n = 8) are not included these calculations. If no statistical difference was noted between children in the 4–8 year old category compared to the 9–14 year old category, the results were combined.</p>c<p>Geometric mean parasite density per mm<sup>3</sup>.</p>", "links"=>[], "tags"=>["immunology", "Infectious diseases", "physiology"], "article_id"=>353905, "categories"=>["Physiology", "Infectious Diseases", "Immunology"], "users"=>["Kirsten E. Lyke", "Abdoulaye Dabo", "Charles Arama", "Modibo Daou", "Issa Diarra", "Amy Wang", "Christopher V. Plowe", "Ogobara K. Doumbo", "Marcelo B. Sztein"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031647.t001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Demographics_/353905", "title"=>"Demographics.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-02-14 01:05:05"}
  • {"files"=>["https://ndownloader.figshare.com/files/683053"], "description"=>"<p>Quantification of T regulatory cells gated on CD3<sup>+</sup>ViViD<sup>−</sup>CD19<sup>−</sup>CD4<sup>+</sup> with representative plots depicting the percentage of CD25<sup>hi</sup> and FOXP3<sup>+</sup> expression (closed histogram) in (a) a child with <i>S. haematobium</i> and concomitant <i>P. falciparum</i> malaria (SP Mal) and (b) a child with <i>P. falciparum</i> malaria (SN Mal) alone. The percentages of gated populations are denoted in each filled histogram (a, b). Region placement was aided by fluorescence minus one (FMO) determinations for CD69<sup>+</sup> and FOXP3<sup>+</sup> cells (open histogram). Dot plots of percentage of CD3<sup>+</sup>ViViD<sup>−</sup>CD19<sup>−</sup>CD4<sup>+</sup>CD69<sup>−</sup>CD25<sup>hi</sup>FOXP3<sup>+</sup> expression and segregated by group and season are depicted in children (c) aged 4–14 years, (d) aged 4–8 years and (e) aged 9–14 years. Each dot represents one individual. Bars represent the median and asterisks depict statistically significant differences between the indicated subset of volunteers and SP children during the transmission season (paired student T test with level of significance set at P<0.05).</p>", "links"=>[], "tags"=>["immunology", "Infectious diseases", "physiology"], "article_id"=>353532, "categories"=>["Physiology", "Infectious Diseases", "Immunology"], "users"=>["Kirsten E. Lyke", "Abdoulaye Dabo", "Charles Arama", "Modibo Daou", "Issa Diarra", "Amy Wang", "Christopher V. Plowe", "Ogobara K. Doumbo", "Marcelo B. Sztein"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031647.g001", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_T_regulatory_cell_detection_/353532", "title"=>"T regulatory cell detection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-02-14 00:58:52"}
  • {"files"=>["https://ndownloader.figshare.com/files/683289"], "description"=>"<p>Shown are the geometric mean lymphocyte proliferative responses as determined by [<sup>3</sup>H]-thymidine incorporation to malaria and schistosoma antigen pool stimulation (4a and b) in PBMC collected during the malaria transmission season and again in the dry season in children with (SP Mal, n = 20) and children without (SN Mal, n = 17) <i>S. haematobium</i>. Responders refer to those individuals with significant proliferative responses to malaria antigen stimulation (n = 8 SP Mal and n = 6 SN Mal, <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031647#pone-0031647-g004\" target=\"_blank\">Figure 4a</a>) or to schistosoma antigen stimulation during the transmission season (n = 13 SP Mal and n = 1 SN Mal, <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031647#pone-0031647-g004\" target=\"_blank\">Figure 4b</a>), with their subsequent dry season values depicted. The dotted line depicts the minimally significant SI of 2.0. The asterix depicts significant differences between SP Mal and SN Mal (P<0.001). No differences were noted between mock or anti-CD25<sup>hi</sup> depletion experiments (not shown).</p>", "links"=>[], "tags"=>["responses", "malaria", "schistosoma"], "article_id"=>353770, "categories"=>["Physiology", "Infectious Diseases", "Immunology"], "users"=>["Kirsten E. Lyke", "Abdoulaye Dabo", "Charles Arama", "Modibo Daou", "Issa Diarra", "Amy Wang", "Christopher V. Plowe", "Ogobara K. Doumbo", "Marcelo B. Sztein"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031647.g004", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Proliferative_responses_to_malaria_and_schistosoma_antigens_/353770", "title"=>"Proliferative responses to malaria and schistosoma antigens.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-02-14 01:02:50"}
  • {"files"=>["https://ndownloader.figshare.com/files/683139"], "description"=>"<p>Representative example of intracellular cytokine (IL-2 and IFN-γ) detection in PBMC, from a child with concomitant <i>S. haematobium</i> and <i>P. falciparum</i> infection, in response to both malaria and schistosoma pooled antigen stimulation and media control for comparison (panel a). Mean intracellular cytokine production from PBMC stimulated with pooled (b) malaria and (c) schistosoma antigens collected in children aged 4–14 years with (SP Mal) and without S. <i>haematobium</i> (SN Mal) measured during the transmission and follow-up dry season. Cytokine-producing cells were found to be predominantly CD3<sup>+</sup>CD19<sup>−</sup>CD4<sup>+</sup>CD8<sup>−</sup> T cells. Cytokine expression is reported as net % cytokine producing cells (stimulant minus media control) and standard deviations.</p>", "links"=>[], "tags"=>["cytokine", "malaria", "schistosoma"], "article_id"=>353624, "categories"=>["Physiology", "Infectious Diseases", "Immunology"], "users"=>["Kirsten E. Lyke", "Abdoulaye Dabo", "Charles Arama", "Modibo Daou", "Issa Diarra", "Amy Wang", "Christopher V. Plowe", "Ogobara K. Doumbo", "Marcelo B. Sztein"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031647.g002", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Intracellular_cytokine_production_to_malaria_and_schistosoma_antigens_/353624", "title"=>"Intracellular cytokine production to malaria and schistosoma antigens.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-02-14 01:00:24"}
  • {"files"=>["https://ndownloader.figshare.com/files/683213"], "description"=>"<p>Representative example of intracellular cytokine detection in PBMC, from a child with concomitant <i>S. haematobium</i> and <i>P. falciparum</i> infection, mock or anti-CD25<sup>hi</sup> depleted prior to stimulation with malaria or schistosoma antigenic pools. Removal of regulatory T cells appears to reverse suppressed immunologic responses resulting in enhanced intracellular IL-2 and IFN-γ in the anti-CD25hi depleted cell population. Media controls are included for comparison.</p>", "links"=>[], "tags"=>["cytokine", "malaria", "schistosoma", "antigens"], "article_id"=>353697, "categories"=>["Physiology", "Infectious Diseases", "Immunology"], "users"=>["Kirsten E. Lyke", "Abdoulaye Dabo", "Charles Arama", "Modibo Daou", "Issa Diarra", "Amy Wang", "Christopher V. Plowe", "Ogobara K. Doumbo", "Marcelo B. Sztein"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031647.g003", "stats"=>{"downloads"=>0, "page_views"=>1, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Intracellular_cytokine_production_to_malaria_and_schistosoma_antigens_after_T_regulatory_cell_depletion_/353697", "title"=>"Intracellular cytokine production to malaria and schistosoma antigens after T regulatory cell depletion.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2012-02-14 01:01:37"}
  • {"files"=>["https://ndownloader.figshare.com/files/683386"], "description"=>"<p><a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0031647#s3\" target=\"_blank\">Results</a> of intracellular cytokine expression after antigenic stimulation of PBMC acquired from age-matched children with (SP Mal) or without <i>S. haematobium</i> (SN Mal) during the malaria transmission (wet) season at the time of a malaria episode and again during a dry season follow-up visit. The numerator results represent those individuals with statistically significant increases in the percentage of cytokine expressed compared to media controls after PBMC stimulation and the denomenator represents the total number of individual PBMC samples analyzed.</p>a<p>PBMC were stimulated with a malaria antigen pool (Apical Membrane antigen 1 and Merozoite Surface Protein 1) or with a <i>S. haematobium</i> pool (soluble egg antigen and soluble worm antigen protein). SP no Mal children were not included in this analysis.</p>b<p>χ<sup>2</sup> analysis, using Mantel-Haenszel or Fisher Exact (two-tailed) as appropriate, was performed between <i>S. haematobium</i> positive (SP Mal) vs. <i>S. haematobium</i> negative (SN Mal) children in each age category. P value significance set at <0.05. Not significant  =  ns.</p>c<p>Three experiments were excluded due to insufficient or poor viability cell quantities to allow proper interpretation of data.</p>d<p>IL-2 and IFN-g production was noted in one SN individual. Urine was negative for eggs both at enrollment and at dry season follow-up suggesting a false positive result.</p>", "links"=>[], "tags"=>["cytokine", "antigen"], "article_id"=>353865, "categories"=>["Physiology", "Infectious Diseases", "Immunology"], "users"=>["Kirsten E. Lyke", "Abdoulaye Dabo", "Charles Arama", "Modibo Daou", "Issa Diarra", "Amy Wang", "Christopher V. Plowe", "Ogobara K. Doumbo", "Marcelo B. Sztein"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0031647.t002", "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Intracellular_Cytokine_Expression_to_Antigen_Stimulation_/353865", "title"=>"Intracellular Cytokine Expression to Antigen Stimulation.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2012-02-14 01:04:25"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"6", "full-text"=>"16", "pdf"=>"1", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"4", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"6"}
  • {"unique-ip"=>"3", "full-text"=>"3", "pdf"=>"3", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2014", "month"=>"4"}
  • {"unique-ip"=>"16", "full-text"=>"8", "pdf"=>"7", "abstract"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"4", "year"=>"2014", "month"=>"10"}
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