Rute Marques, Adam Williams, Urszula Eksmond, Andy Wullaert, Nigel Killeen, Manolis Pasparakis, Dimitris Kioussis, George Kassiotis
Background: In addition to progressive CD4(+) T cell immune deficiency, HIV infection is characterized by generalized immune activation, thought to arise from increased microbial exposure resulting from diminishing immunity.
Results: Here we report that, in a virus-free mouse model, conditional ablation of activated CD4(+) T cells, the targets of immunodeficiency viruses, accelerates their turnover and produces CD4(+) T cell immune deficiency. More importantly, activated CD4(+) T cell killing also results in generalized immune activation, which is attributable to regulatory CD4(+) T cell insufficiency and preventable by regulatory CD4(+) T cell reconstitution. Immune activation in this model develops independently of microbial exposure. Furthermore, microbial translocation in mice with conditional disruption of intestinal epithelial integrity affects myeloid but not T cell homeostasis.
Conclusions: Although neither ablation of activated CD4(+) T cells nor disruption of intestinal epithelial integrity in mice fully reproduces every aspect of HIV-associated immune dysfunction in humans, ablation of activated CD4(+) T cells, but not disruption of intestinal epithelial integrity, approximates the two key immune alterations in HIV infection: CD4(+) T cell immune deficiency and generalized immune activation. We therefore propose activated CD4(+) T cell killing as a common etiology for both immune deficiency and activation in HIV infection.
{"title":"Generalized immune activation as a direct result of activated CD4+ T cell killing.","authors":"Rute Marques, Adam Williams, Urszula Eksmond, Andy Wullaert, Nigel Killeen, Manolis Pasparakis, Dimitris Kioussis, George Kassiotis","doi":"10.1186/jbiol194","DOIUrl":"https://doi.org/10.1186/jbiol194","url":null,"abstract":"<p><strong>Background: </strong>In addition to progressive CD4(+) T cell immune deficiency, HIV infection is characterized by generalized immune activation, thought to arise from increased microbial exposure resulting from diminishing immunity.</p><p><strong>Results: </strong>Here we report that, in a virus-free mouse model, conditional ablation of activated CD4(+) T cells, the targets of immunodeficiency viruses, accelerates their turnover and produces CD4(+) T cell immune deficiency. More importantly, activated CD4(+) T cell killing also results in generalized immune activation, which is attributable to regulatory CD4(+) T cell insufficiency and preventable by regulatory CD4(+) T cell reconstitution. Immune activation in this model develops independently of microbial exposure. Furthermore, microbial translocation in mice with conditional disruption of intestinal epithelial integrity affects myeloid but not T cell homeostasis.</p><p><strong>Conclusions: </strong>Although neither ablation of activated CD4(+) T cells nor disruption of intestinal epithelial integrity in mice fully reproduces every aspect of HIV-associated immune dysfunction in humans, ablation of activated CD4(+) T cells, but not disruption of intestinal epithelial integrity, approximates the two key immune alterations in HIV infection: CD4(+) T cell immune deficiency and generalized immune activation. We therefore propose activated CD4(+) T cell killing as a common etiology for both immune deficiency and activation in HIV infection.</p>","PeriodicalId":15075,"journal":{"name":"Journal of Biology","volume":"8 10","pages":"93"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/jbiol194","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28533118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-01-01Epub Date: 2009-08-05DOI: 10.1186/jbiol166
Rick M Maizels
Parasites are accomplished evaders of host immunity. Their evasion strategies have shaped every facet of the immune system, driving diversity within gene families and immune gene polymorphisms within populations. New studies published recently in BMC Biology and Journal of Experimental Medicine document parasite-associated immunosuppression in natural populations and suggest that host genetic variants favoring resistance to parasites may be detrimental in the absence of infection.
{"title":"Parasite immunomodulation and polymorphisms of the immune system.","authors":"Rick M Maizels","doi":"10.1186/jbiol166","DOIUrl":"https://doi.org/10.1186/jbiol166","url":null,"abstract":"<p><p>Parasites are accomplished evaders of host immunity. Their evasion strategies have shaped every facet of the immune system, driving diversity within gene families and immune gene polymorphisms within populations. New studies published recently in BMC Biology and Journal of Experimental Medicine document parasite-associated immunosuppression in natural populations and suggest that host genetic variants favoring resistance to parasites may be detrimental in the absence of infection.</p>","PeriodicalId":15075,"journal":{"name":"Journal of Biology","volume":" ","pages":"62"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/jbiol166","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40019527","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Expressed sequence tag analyses of the annelid Pomatoceros lamarckii, recently published in BMC Evolutionary Biology, are consistent with less extensive gene loss in the Lophotrochozoa than in the Ecdysozoa, but it would be premature to generalize about patterns of gene loss on the basis of the limited data available.
{"title":"The gene complement of the ancestral bilaterian - was Urbilateria a monster?","authors":"David J Miller, Eldon E Ball","doi":"10.1186/jbiol192","DOIUrl":"https://doi.org/10.1186/jbiol192","url":null,"abstract":"<p><p>Expressed sequence tag analyses of the annelid Pomatoceros lamarckii, recently published in BMC Evolutionary Biology, are consistent with less extensive gene loss in the Lophotrochozoa than in the Ecdysozoa, but it would be premature to generalize about patterns of gene loss on the basis of the limited data available.</p>","PeriodicalId":15075,"journal":{"name":"Journal of Biology","volume":"8 10","pages":"89"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/jbiol192","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28529655","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nienke Vrisekoop, Judith N Mandl, Ronald N Germain
Detailed analysis of T cell dynamics in humans is challenging and mouse models can be important tools for characterizing T cell dynamic processes. In a paper just published in Journal of Biology, Marques et al. suggest that a mouse model with its activated CD4(+) T cells are deleted has relevance for HIV infection.
{"title":"Life and death as a T lymphocyte: from immune protection to HIV pathogenesis.","authors":"Nienke Vrisekoop, Judith N Mandl, Ronald N Germain","doi":"10.1186/jbiol198","DOIUrl":"https://doi.org/10.1186/jbiol198","url":null,"abstract":"<p><p>Detailed analysis of T cell dynamics in humans is challenging and mouse models can be important tools for characterizing T cell dynamic processes. In a paper just published in Journal of Biology, Marques et al. suggest that a mouse model with its activated CD4(+) T cells are deleted has relevance for HIV infection.</p>","PeriodicalId":15075,"journal":{"name":"Journal of Biology","volume":"8 10","pages":"91"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/jbiol198","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28539674","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-01-01Epub Date: 2009-12-14DOI: 10.1186/jbiol203
Marc Ouellette, Barbara Papadopoulou
The regulation of gene expression in trypanosomes is unique. In the absence of transcriptional control at the level of initiation, a subset of Trypanosoma brucei genes form post-transcriptional regulons in which mRNAs are co-regulated in response to differentiation signals. See research articles http://www.biomedcentral.com/1471-2164/10/427, http://www.biomedcentral.com/1471-2164/10/482 and http://www.biomedcentral.com/1471-2164/10/495.
{"title":"Coordinated gene expression by post-transcriptional regulons in African trypanosomes.","authors":"Marc Ouellette, Barbara Papadopoulou","doi":"10.1186/jbiol203","DOIUrl":"https://doi.org/10.1186/jbiol203","url":null,"abstract":"<p><p>The regulation of gene expression in trypanosomes is unique. In the absence of transcriptional control at the level of initiation, a subset of Trypanosoma brucei genes form post-transcriptional regulons in which mRNAs are co-regulated in response to differentiation signals. See research articles http://www.biomedcentral.com/1471-2164/10/427, http://www.biomedcentral.com/1471-2164/10/482 and http://www.biomedcentral.com/1471-2164/10/495.</p>","PeriodicalId":15075,"journal":{"name":"Journal of Biology","volume":"8 11","pages":"100"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/jbiol203","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28600476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-01-01Epub Date: 2009-01-20DOI: 10.1186/jbiol109
Tom Price, Zenobia Lewis, Nina Wedell
Sperm from Drosophila simulans that carry a sex-ratio distorter is preferentially lost from females' sperm-storage organs. This suggests that sperm dumping is a major factor affecting sperm competition in this species, and may have evolved in response to sex-ratio distorters.
{"title":"Sperm dumping as a defense against meiotic drive.","authors":"Tom Price, Zenobia Lewis, Nina Wedell","doi":"10.1186/jbiol109","DOIUrl":"https://doi.org/10.1186/jbiol109","url":null,"abstract":"<p><p>Sperm from Drosophila simulans that carry a sex-ratio distorter is preferentially lost from females' sperm-storage organs. This suggests that sperm dumping is a major factor affecting sperm competition in this species, and may have evolved in response to sex-ratio distorters.</p>","PeriodicalId":15075,"journal":{"name":"Journal of Biology","volume":"8 1","pages":"6"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/jbiol109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27985230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-01-01Epub Date: 2009-01-23DOI: 10.1186/jbiol110
Patrick Forterre, Simonetta Gribaldo, Céline Brochier-Armanet
The complete genome sequence of the crenarchaeon Ignicoccus hospitalis published recently in Genome Biology provides a great leap forward in the dissection of its unique association with another hyperthermophilic archaeon, Nanoarchaeum equitans.
{"title":"Happy together: genomic insights into the unique Nanoarchaeum/Ignicoccus association.","authors":"Patrick Forterre, Simonetta Gribaldo, Céline Brochier-Armanet","doi":"10.1186/jbiol110","DOIUrl":"https://doi.org/10.1186/jbiol110","url":null,"abstract":"<p><p>The complete genome sequence of the crenarchaeon Ignicoccus hospitalis published recently in Genome Biology provides a great leap forward in the dissection of its unique association with another hyperthermophilic archaeon, Nanoarchaeum equitans.</p>","PeriodicalId":15075,"journal":{"name":"Journal of Biology","volume":"8 1","pages":"7"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/jbiol110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27985675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-01-01Epub Date: 2009-04-06DOI: 10.1186/jbiol129
Heike Feldhaar, Roy Gross
The obligate intracellular bacterial endosymbionts of insects are a paradigm for reductive genome evolution. A study published recently in BMC Biology demonstrates that similar evolutionary forces shaping genome structure may also apply to extracellular endosymbionts.
{"title":"Genome degeneration affects both extracellular and intracellular bacterial endosymbionts.","authors":"Heike Feldhaar, Roy Gross","doi":"10.1186/jbiol129","DOIUrl":"https://doi.org/10.1186/jbiol129","url":null,"abstract":"<p><p>The obligate intracellular bacterial endosymbionts of insects are a paradigm for reductive genome evolution. A study published recently in BMC Biology demonstrates that similar evolutionary forces shaping genome structure may also apply to extracellular endosymbionts.</p>","PeriodicalId":15075,"journal":{"name":"Journal of Biology","volume":"8 3","pages":"31"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/jbiol129","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28243661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-01-01Epub Date: 2009-04-15DOI: 10.1186/jbiol132
Thiago M Venancio, L Aravind
Reconstruction of transcriptional regulatory networks of uncharacterized bacteria is a main challenge for the post-genomic era. Recent studies, including one in BMC Systems Biology, address this problem in the relatively underexplored actinobacteria clade, which includes major pathogenic and economically relevant taxa.
{"title":"Reconstructing prokaryotic transcriptional regulatory networks: lessons from actinobacteria.","authors":"Thiago M Venancio, L Aravind","doi":"10.1186/jbiol132","DOIUrl":"https://doi.org/10.1186/jbiol132","url":null,"abstract":"<p><p>Reconstruction of transcriptional regulatory networks of uncharacterized bacteria is a main challenge for the post-genomic era. Recent studies, including one in BMC Systems Biology, address this problem in the relatively underexplored actinobacteria clade, which includes major pathogenic and economically relevant taxa.</p>","PeriodicalId":15075,"journal":{"name":"Journal of Biology","volume":"8 3","pages":"29"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1186/jbiol132","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28243666","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2009-01-01Epub Date: 2009-04-16DOI: 10.1186/jbiol130
Esther T Chan, Gerald T Quon, Gordon Chua, Tomas Babak, Miles Trochesset, Ralph A Zirngibl, Jane Aubin, Michael J H Ratcliffe, Andrew Wilde, Michael Brudno, Quaid D Morris, Timothy R Hughes
Background: Vertebrates share the same general body plan and organs, possess related sets of genes, and rely on similar physiological mechanisms, yet show great diversity in morphology, habitat and behavior. Alteration of gene regulation is thought to be a major mechanism in phenotypic variation and evolution, but relatively little is known about the broad patterns of conservation in gene expression in non-mammalian vertebrates.
Results: We measured expression of all known and predicted genes across twenty tissues in chicken, frog and pufferfish. By combining the results with human and mouse data and considering only ten common tissues, we have found evidence of conserved expression for more than a third of unique orthologous genes. We find that, on average, transcription factor gene expression is neither more nor less conserved than that of other genes. Strikingly, conservation of expression correlates poorly with the amount of conserved nonexonic sequence, even using a sequence alignment technique that accounts for non-collinearity in conserved elements. Many genes show conserved human/fish expression despite having almost no nonexonic conserved primary sequence.
Conclusions: There are clearly strong evolutionary constraints on tissue-specific gene expression. A major challenge will be to understand the precise mechanisms by which many gene expression patterns remain similar despite extensive cis-regulatory restructuring.
{"title":"Conservation of core gene expression in vertebrate tissues.","authors":"Esther T Chan, Gerald T Quon, Gordon Chua, Tomas Babak, Miles Trochesset, Ralph A Zirngibl, Jane Aubin, Michael J H Ratcliffe, Andrew Wilde, Michael Brudno, Quaid D Morris, Timothy R Hughes","doi":"10.1186/jbiol130","DOIUrl":"10.1186/jbiol130","url":null,"abstract":"<p><strong>Background: </strong>Vertebrates share the same general body plan and organs, possess related sets of genes, and rely on similar physiological mechanisms, yet show great diversity in morphology, habitat and behavior. Alteration of gene regulation is thought to be a major mechanism in phenotypic variation and evolution, but relatively little is known about the broad patterns of conservation in gene expression in non-mammalian vertebrates.</p><p><strong>Results: </strong>We measured expression of all known and predicted genes across twenty tissues in chicken, frog and pufferfish. By combining the results with human and mouse data and considering only ten common tissues, we have found evidence of conserved expression for more than a third of unique orthologous genes. We find that, on average, transcription factor gene expression is neither more nor less conserved than that of other genes. Strikingly, conservation of expression correlates poorly with the amount of conserved nonexonic sequence, even using a sequence alignment technique that accounts for non-collinearity in conserved elements. Many genes show conserved human/fish expression despite having almost no nonexonic conserved primary sequence.</p><p><strong>Conclusions: </strong>There are clearly strong evolutionary constraints on tissue-specific gene expression. A major challenge will be to understand the precise mechanisms by which many gene expression patterns remain similar despite extensive cis-regulatory restructuring.</p>","PeriodicalId":15075,"journal":{"name":"Journal of Biology","volume":"8 3","pages":"33"},"PeriodicalIF":0.0,"publicationDate":"2009-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2689434/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"28113335","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}