About: Transcriptional profiling of the spleen in progressive visceral leishmaniasis reveals mixed expression of type 1 and type 2 cytokine-responsive genes

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About: Transcriptional profiling of the spleen in progressive visceral leishmaniasis reveals mixed expression of type 1 and type 2 cytokine-responsive genes Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Transcriptional profiling of the spleen in progressive visceral leishmaniasis reveals mixed expression of type 1 and type 2 cytokine-responsive genes
Creator	Band, Mark Cappello, Michael Hernandez, Alvaro Pekosz, Andrew Espitia, Claudia Medina, Audrie Melby, Peter Osorio, Yaneth Patel, Mandakini Saldarriaga, Omar Travi, Bruno
Source	Medline; PMC
abstract	BACKGROUND: The Syrian golden hamster (Mesocricetus aureus) has been used as a model to study infections caused by a number of human pathogens. Studies of immunopathogenesis in hamster infection models are challenging because of the limited availability of reagents needed to define cellular and molecular determinants. RESULTS: We sequenced a hamster cDNA library and developed a first-generation custom cDNA microarray that included 5131 unique cDNAs enriched for immune response genes. We used this microarray to interrogate the hamster spleen response to Leishmania donovani, an intracellular protozoan that causes visceral leishmaniasis. The hamster model of visceral leishmaniasis is of particular interest because it recapitulates clinical and immunopathological features of human disease, including cachexia, massive splenomegaly, pancytopenia, immunosuppression, and ultimately death. In the microarray a differentially expressed transcript was identified as having at least a 2-fold change in expression between uninfected and infected groups and a False Discovery Rate of <5%. Following a relatively silent early phase of infection (at 7 and 14 days post-infection only 8 and 24 genes, respectively, were differentially expressed), there was dramatic upregulation of inflammatory and immune-related genes in the spleen (708 differentially expressed genes were evident at 28 days post-infection). The differentially expressed transcripts included genes involved in inflammation, immunity, and immune cell trafficking. Of particular interest there was concomitant upregulation of the IFN-γ and interleukin (IL)-4 signaling pathways, with increased expression of a battery of IFN-γ- and IL-4-responsive genes. The latter included genes characteristic of alternatively activated macrophages. CONCLUSIONS: Transcriptional profiling was accomplished in the Syrian golden hamster, for which a fully annotated genome is not available. In the hamster model of visceral leishmaniasis, a robust and functional IFN-γ response did not restrain parasite load and progression of disease. This supports the accumulating evidence that macrophages are ineffectively activated to kill the parasite. The concomitant expression of IL-4/IL-13 and their downstream target genes, some of which were characteristic of alternative macrophage activation, are likely to contribute to this. Further dissection of mechanisms that lead to polarization of macrophages toward a permissive state is needed to fully understand the pathogenesis of visceral leishmaniasis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12865-014-0038-z) contains supplementary material, which is available to authorized users.
has issue date	2014-11-26(xsd:dateTime)
bibo:doi	10.1186/s12865-014-0038-z
bibo:pmid	25424735
has license	cc-by
sha1sum (hex)	85172df4b29cb30c4e98011ed79e9da2ca63fbd6
schema:url	https://doi.org/10.1186/s12865-014-0038-z
resource representing a document's title	Transcriptional profiling of the spleen in progressive visceral leishmaniasis reveals mixed expression of type 1 and type 2 cytokine-responsive genes
has PubMed Central identifier	PMC4253007
has PubMed identifier	25424735
schema:publication	BMC Immunol
resource representing a document's body	covid:85172df4b29cb30c4e98011ed79e9da2ca63fbd6#body_text
is schema:about of	named entity 'TRANSCRIPTIONAL PROFILING' named entity 'CAUSED BY' named entity 'MODELS' named entity 'EXPRESSION' named entity 'TYPE 1' named entity 'TYPE 2' named entity 'NUMBER OF' named entity 'PATHOGENS' named entity 'STUDY' named entity 'MIXED' named entity 'USED' named entity 'CELLULAR' named entity 'GENES' named entity 'SPLEEN' named entity 'CYTOKINE' named entity 'PROGRESSIVE' named entity 'RESPONSIVE' named entity 'SYRIAN GOLDEN HAMSTER' named entity 'IMMUNOPATHOGENESIS' named entity 'MODEL' named entity 'STUDIES' named entity 'DETERMINANTS' named entity 'HUMAN' named entity 'HAMSTER' named entity 'BACKGROUND' named entity 'VISCERAL LEISHMANIASIS' named entity 'NEEDED' named entity 'REAGENTS' named entity 'INFECTIONS' named entity 'INFECTION' named entity 'AVAILABILITY OF' named entity 'REVEALS' named entity 'LIMITED' named entity 'MOLECULAR' covid:arg/85172df4b29cb30c4e98011ed79e9da2ca63fbd6 named entity 'hamster' named entity 'type 2 cytokine' named entity 'spleen' named entity 'type 1' named entity 'peritoneal' named entity 'hamster' named entity 'promastigotes' named entity 'lymph node' named entity 'PCR' named entity 'RNA' named entity 'biological functions' named entity 'microarray analysis' named entity 'Hamster' named entity 'M2 macrophage' named entity 'RNA' named entity 'infection' named entity 'hamster' named entity 'infection' named entity 'West Nile virus' named entity 'serum' named entity 'intron' named entity 'EST' named entity 'gene' named entity 'Leishmania' named entity 'p-value' named entity 'Institutional Animal Care and Use Committee' named entity 'L. infantum' named entity 'cloned' named entity 'Andes virus' named entity 'hamster' named entity 'Cxcl10' named entity 'IL-4' named entity 'mice' named entity 'infection' named entity 'cDNA library' named entity 'tryptophan'

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