BALB/c Mice Deficient in CD4+ T Cell IL-4Rα Expression Control Leishmania mexicana Load although Female but Not Male Mice Develop a Healer Phenotype
Publication Date
January 04, 2011
Journal
PLOS Neglected Tropical Diseases
Authors
Karen J. Bryson, Owain R. Millington, Thabang Mokgethi, H. Adrienne Mc Gachy, et al
Volume
5
Issue
1
Pages
e930
DOI
https://dx.plos.org/10.1371/journal.pntd.0000930
Publisher URL
http://journals.plos.org/plosntds/article?id=10.1371%2Fjournal.pntd.0000930
PubMed
http://www.ncbi.nlm.nih.gov/pubmed/21245915
PubMed Central
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3014948
Europe PMC
http://europepmc.org/abstract/MED/21245915
Web of Science
000286596000008
Scopus
79851491375
Mendeley
http://www.mendeley.com/research/balbc-mice-deficient-cd4-t-cell-il4r%CE%B1-expression-control-leishmania-mexicana-load-although-female-no
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Mendeley | Further Information

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Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/403463", "https://ndownloader.figshare.com/files/403478", "https://ndownloader.figshare.com/files/403486"], "description"=>"<div><p>Immunologically intact BALB/c mice infected with <em>Leishmania mexicana</em> develop non-healing progressively growing lesions associated with a biased Th2 response while similarly infected IL-4Rα-deficient mice fail to develop lesions and develop a robust Th1 response. In order to determine the functional target(s) for IL-4/IL-13 inducing non-healing disease, the course of <em>L. mexicana</em> infection was monitored in mice lacking IL-4Rα expression in specific cellular compartments. A deficiency of IL-4Rα expression on macrophages/neutrophils (in LysM<sup>cre</sup>IL-4Rα<sup>−/lox</sup> animals) had minimal effect on the outcome of <em>L. mexicana</em> infection compared with control (IL-4Rα<sup>−/flox</sup>) mice. In contrast, CD4<sup>+</sup> T cell specific (Lck<sup>cre</sup>IL-4Rα<sup>−/lox</sup>) IL-4Rα<sup>−/−</sup> mice infected with <em>L. mexicana</em> developed small lesions, which subsequently healed in female mice, but persisted in adult male mice. While a strong Th1 response was manifest in both male and female CD4<sup>+</sup> T cell specific IL-4Rα<sup>−/−</sup> mice infected with <em>L. mexicana</em>, induction of IL-4 was manifest in males but not females, independently of CD4<sup>+</sup> T cell IL-4 responsiveness. Similar results were obtained using pan-T cell specific (iLck<sup>cre</sup>IL-4Rα<sup>−/lox</sup>) IL-4Rα<sup>−/−</sup> mice. Collectively these data demonstrate that upon infection with <em>L. mexicana</em>, initial lesion growth in BALB/c mice is dependent on non-T cell population(s) responsive to IL-4/IL-13 while progressive infection is dependent on CD4<sup>+</sup> T cells responsive to IL-4.</p></div>", "links"=>[], "tags"=>["mice", "deficient", "healer", "phenotype"], "article_id"=>139713, "categories"=>["Immunology"], "users"=>["Karen J. Bryson", "Owain R. Millington", "Thabang Mokgethi", "H. Adrienne McGachy", "Frank Brombacher", "James Alexander"], "doi"=>["https://dx.doi.org/10.1371/journal.pntd.0000930.s001", "https://dx.doi.org/10.1371/journal.pntd.0000930.s002", "https://dx.doi.org/10.1371/journal.pntd.0000930.s003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/BALB_c_Mice_Deficient_in_CD4_T_Cell_IL_4R_Expression_Control_Leishmania_mexicana_Load_although_Female_but_Not_Male_Mice_Develop_a_Healer_Phenotype/139713", "title"=>"BALB/c Mice Deficient in CD4<sup>+</sup> T Cell IL-4Rα Expression Control <em>Leishmania mexicana</em> Load although Female but Not Male Mice Develop a Healer Phenotype", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2011-01-04 02:41:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/807971"], "description"=>"<p>Mean lesion growth (Figure. 1A), parasite burdens (Figure. 1B), and <i>L. mexicana</i> antigen induced (25 µg/ml) splenocyte IFN-γ (Figure. 1C), and IL-4 (Figure 1D) produced from IL-4Rα intact (IL-4Rα<sup>−/lox</sup>), macrophage/neutrophil specific (LysM<sup>cre</sup>IL-4Rα<sup>−/lox</sup>) IL-4Rα<sup>−/−</sup>, and global IL-4Rα<sup>−/−</sup> mice infected sub-cutaneously with 5×10<sup>6</sup> amastigotes of <i>L. mexicana</i>. At 12 weeks post infection parasite burdens were significantly less in IL-4Rα<sup>−/−</sup> mice than IL-4Rα<sup>−/lox</sup> or LysM<sup>cre</sup>IL-4Rα<sup>−/lox</sup> mice (****p<0.0001) and IFN-γ production significantly greater (**p<0.01). Results are mean +/− s.e. 5 mice. Representative of 3 independent experiments.</p>", "links"=>[], "tags"=>["deficiency"], "article_id"=>478341, "categories"=>["Immunology"], "users"=>["Karen J. Bryson", "Owain R. Millington", "Thabang Mokgethi", "H. Adrienne McGachy", "Frank Brombacher", "James Alexander"], "doi"=>["https://dx.doi.org/10.1371/journal.pntd.0000930.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IL_4R_deficiency_in_macrophages_neutrophils_does_not_influence_L_mexicana_growth_or_the_immune_response_/478341", "title"=>"IL-4Rα deficiency in macrophages/neutrophils does not influence <i>L. mexicana</i> growth or the immune response.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-01-04 02:19:01"}
  • {"files"=>["https://ndownloader.figshare.com/files/808075"], "description"=>"<p>Mean lesion growth (Figure 2A and B) and parasite burdens at week 12 (Figure 2C and D) in female (Figure 2A and C) and male (Figure 2B and D) IL-4Rα intact (IL-4Rα<sup>−/lox</sup>), CD4<sup>+</sup> T cell specific (Lck<sup>cre</sup>IL-4Rα<sup>−/lox</sup>) IL-4Rα<sup>−/−</sup>, and global IL-4Rα<sup>−/−</sup> mice infected sub-cutaneously with 5×10<sup>6</sup> amastigotes of <i>L. mexicana</i>. Results are mean +/− s.e. 5 mice. Representative of 4 separate experiments. Parasite burdens in IL-4Rα<sup>−/−</sup> male and female mice were significantly less than IL-4Rα intact mice (****p<0.0001) for both male and female mice. Parasite burdens were also significantly less in male and female CD4<sup>+</sup> T cell specific IL-4Rα<sup>−/−</sup> compared with IL-4Rα intact mice (****p<0.0001) for females and (**p<0.01) for males. Male CD4<sup>+</sup> T cell specific IL-4Rα<sup>−/−</sup> had significantly higher parasite burdens than females on the same background (p<0.001).</p>", "links"=>[], "tags"=>["deficiency", "cells", "enables", "parasite"], "article_id"=>478442, "categories"=>["Immunology"], "users"=>["Karen J. Bryson", "Owain R. Millington", "Thabang Mokgethi", "H. Adrienne McGachy", "Frank Brombacher", "James Alexander"], "doi"=>["https://dx.doi.org/10.1371/journal.pntd.0000930.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IL_4R_deficiency_in_CD4_T_cells_enables_control_of_L_mexicana_parasite_growth_/478442", "title"=>"IL-4Rα deficiency in CD4<sup>+</sup> T cells enables control of <i>L. mexicana</i> parasite growth.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-01-04 02:20:42"}
  • {"files"=>["https://ndownloader.figshare.com/files/808171"], "description"=>"<p><i>L. mexicana</i> antigen induced (10 µg/ml) splenocyte IFN-γ (Figure 3A and B), and 6 and 12 week serum IgG2a levels (Figure 3C and 3D) produced from female (Figure 3A and C) and male (Figure 3B and D) IL-4Rα intact (IL-4Rα<sup>−/lox</sup>), CD4<sup>+</sup> T cell specific (Lck<sup>cre</sup>IL-4Rα<sup>−/lox</sup>) IL-4Rα<sup>−/−</sup>, and global IL-4Rα<sup>−/−</sup> mice infected sub-cutaneously with 5×10<sup>6</sup> amastigotes of <i>L. mexicana</i>. *p<0.05, **p<0.01 compared with IL-4Rα intact mice. Representative of 4 separate experiments.</p>", "links"=>[], "tags"=>["deficiency", "cells", "enhanced", "th1", "responses"], "article_id"=>478534, "categories"=>["Immunology"], "users"=>["Karen J. Bryson", "Owain R. Millington", "Thabang Mokgethi", "H. Adrienne McGachy", "Frank Brombacher", "James Alexander"], "doi"=>["https://dx.doi.org/10.1371/journal.pntd.0000930.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IL_4R_deficiency_in_CD4_T_cells_results_in_enhanced_Th1_responses_after_L_mexicana_infection_/478534", "title"=>"IL-4Rα deficiency in CD4<sup>+</sup> T cells results in enhanced Th1 responses after <i>L. mexicana</i> infection.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-01-04 02:22:14"}
  • {"files"=>["https://ndownloader.figshare.com/files/808304"], "description"=>"<p><i>L. mexicana</i> antigen induced (10 µg/ml) splenocyte IL-4 (Figure 4A and B), IL-5 (Figure 4C and D) and IL-10 (Figure 4E and F) produced from female (Figure 4A, C and E) and male (Figure 4B, D and F) IL-4Rα intact (IL-4Rα<sup>−/lox</sup>), CD4<sup>+</sup> T cell specific (Lck<sup>cre</sup>IL-4Rα<sup>−/lox</sup>) IL-4Rα<sup>−/−</sup>, and global IL-4Rα<sup>−/−</sup> mice infected sub-cutaneously with 5×10<sup>6</sup> amastigotes of <i>L. mexicana</i>. *p<0.05, **p<0.01 compared with IL-4Rα intact mice. Representative of 4 separate experiments.</p>", "links"=>[], "tags"=>["deficiency", "cells", "th2", "responses"], "article_id"=>478673, "categories"=>["Immunology"], "users"=>["Karen J. Bryson", "Owain R. Millington", "Thabang Mokgethi", "H. Adrienne McGachy", "Frank Brombacher", "James Alexander"], "doi"=>["https://dx.doi.org/10.1371/journal.pntd.0000930.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IL_4R_deficiency_in_CD4_T_cells_results_in_decreased_specific_Th2_responses_in_female_mice_/478673", "title"=>"IL-4Rα deficiency in CD4<sup>+</sup> T cells results in decreased specific Th2 responses in female mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-01-04 02:24:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/808461"], "description"=>"<p>ConA and anti-CD3 induced (10 µg/ml) splenocyte IL-4 produced from female (Figure 5A) and male (Figure 5B) IL-4Rα intact (IL-4Rα<sup>−/lox</sup>), CD4<sup>+</sup> T cell specific (Lck<sup>cre</sup>IL-4Rα<sup>−/lox</sup>) IL-4Rα<sup>−/−</sup>, and global IL-4Rα<sup>−/−</sup> mice infected sub-cutaneously with 5×10<sup>6</sup> amastigotes of <i>L. mexicana</i> 12 weeks previously. *p<0.05, **p<0.01 compared with IL-4Rα intact mice. IL-4 production from female Lck<sup>cre</sup>IL-4Rα<sup>−/lox</sup> mice was significantly less than similarly treated male Lck<sup>cre</sup>IL-4Rα<sup>−/lox</sup> mice (p<0.02 for ConA and p<0.05 for anti-CD3 respectively). Results are mean+/− s.e. 5 mice. Representative of 2 separate experiments.</p>", "links"=>[], "tags"=>["deficiency", "cells", "non-specific", "th2", "responses"], "article_id"=>478826, "categories"=>["Immunology"], "users"=>["Karen J. Bryson", "Owain R. Millington", "Thabang Mokgethi", "H. Adrienne McGachy", "Frank Brombacher", "James Alexander"], "doi"=>["https://dx.doi.org/10.1371/journal.pntd.0000930.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_IL_4R_deficiency_in_CD4_T_cells_results_in_decreased_non_specific_Th2_responses_in_female_mice_/478826", "title"=>"IL-4Rα deficiency in CD4<sup>+</sup> T cells results in decreased non-specific Th2 responses in female mice.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-01-04 02:27:06"}
  • {"files"=>["https://ndownloader.figshare.com/files/808555"], "description"=>"<p>Cytokine production by CD4<sup>+</sup> T cells from draining lymph nodes of <i>L. mexicana</i> infected female (Figure 6A and C) and male (Figure 6B and D) IL-4Rα intact (IL-4Rα<sup>/lox</sup>), CD4<sup>+</sup> T cell specific (Lck<sup>cre</sup>IL-4Rα<sup>−/lox</sup>) IL-4Rα<sup>−/−</sup>, and global IL-4Rα<sup>−/−</sup> mice as assessed by flow cytometry at 12 weeks post-infection. Results are mean+/− s.d. 5 mice. Representative of 2 separate experiments.</p>", "links"=>[], "tags"=>["mice"], "article_id"=>478929, "categories"=>["Immunology"], "users"=>["Karen J. Bryson", "Owain R. Millington", "Thabang Mokgethi", "H. Adrienne McGachy", "Frank Brombacher", "James Alexander"], "doi"=>["https://dx.doi.org/10.1371/journal.pntd.0000930.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Infected_female_T_cell_specific_IL_4R_8722_8722_mice_have_less_IL_4_and_more_IFN_947_CD4_cells_/478929", "title"=>"Infected female T cell specific IL-4Rα<sup>−/−</sup> mice have less IL-4<sup>+</sup> and more IFN-γ<sup>+</sup> CD4<sup>+</sup> cells.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2011-01-04 02:28:49"}

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