Modulation of transcriptional and inflammatory responses in murine macrophages by the Mycobacterium tuberculosis mammalian cell entry (Mce) 1 complex.

The outcome of many infections depends on the initial interactions between agent and host. Aiming at elucidating the effect of the M. tuberculosis Mce1 protein complex on host transcriptional and immunological responses to infection with M. tuberculosis, RNA from murine macrophages at 15, 30, 60 min...

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Autores principales: Ruth Stavrum, Anne-Kristin Stavrum, Håvard Valvatne, Lee W Riley, Elling Ulvestad, Inge Jonassen, Jörg Assmus, T Mark Doherty, Harleen M S Grewal
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spelling oai:doaj.org-article:80895a8479bf4a1daf90a098e2e500402021-11-18T07:35:50ZModulation of transcriptional and inflammatory responses in murine macrophages by the Mycobacterium tuberculosis mammalian cell entry (Mce) 1 complex.1932-620310.1371/journal.pone.0026295https://doaj.org/article/80895a8479bf4a1daf90a098e2e500402011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22039457/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203The outcome of many infections depends on the initial interactions between agent and host. Aiming at elucidating the effect of the M. tuberculosis Mce1 protein complex on host transcriptional and immunological responses to infection with M. tuberculosis, RNA from murine macrophages at 15, 30, 60 min, 4 and 10 hrs post-infection with M. tuberculosis H37Rv or Δ-mce1 H37Rv was analyzed by whole-genome microarrays and RT-QPCR. Immunological responses were measured using a 23-plex cytokine assay. Compared to uninfected controls, 524 versus 64 genes were up-regulated by 15 min post H37Rv- and Δ-mce1 H37Rv-infection, respectively. By 15 min post-H37Rv infection, a decline of 17 cytokines combined with up-regulation of Ccl24 (26.5-fold), Clec4a2 (23.2-fold) and Pparγ (10.5-fold) indicated an anti-inflammatory response initiated by IL-13. Down-regulation of Il13ra1 combined with up-regulation of Il12b (30.2-fold), suggested switch to a pro-inflammatory response by 4 hrs post H37Rv-infection. Whereas no significant change in cytokine concentration or transcription was observed during the first hour post Δ-mce1 H37Rv-infection, a significant decline of IL-1b, IL-9, IL-13, Eotaxin and GM-CSF combined with increased transcription of Il12b (25.1-fold) and Inb1 (17.9-fold) by 4 hrs, indicated a pro-inflammatory response. The balance between pro-and anti-inflammatory responses during the early stages of infection may have significant bearing on outcome.Ruth StavrumAnne-Kristin StavrumHåvard ValvatneLee W RileyElling UlvestadInge JonassenJörg AssmusT Mark DohertyHarleen M S GrewalPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 10, p e26295 (2011)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Ruth Stavrum
Anne-Kristin Stavrum
Håvard Valvatne
Lee W Riley
Elling Ulvestad
Inge Jonassen
Jörg Assmus
T Mark Doherty
Harleen M S Grewal
Modulation of transcriptional and inflammatory responses in murine macrophages by the Mycobacterium tuberculosis mammalian cell entry (Mce) 1 complex.
description The outcome of many infections depends on the initial interactions between agent and host. Aiming at elucidating the effect of the M. tuberculosis Mce1 protein complex on host transcriptional and immunological responses to infection with M. tuberculosis, RNA from murine macrophages at 15, 30, 60 min, 4 and 10 hrs post-infection with M. tuberculosis H37Rv or Δ-mce1 H37Rv was analyzed by whole-genome microarrays and RT-QPCR. Immunological responses were measured using a 23-plex cytokine assay. Compared to uninfected controls, 524 versus 64 genes were up-regulated by 15 min post H37Rv- and Δ-mce1 H37Rv-infection, respectively. By 15 min post-H37Rv infection, a decline of 17 cytokines combined with up-regulation of Ccl24 (26.5-fold), Clec4a2 (23.2-fold) and Pparγ (10.5-fold) indicated an anti-inflammatory response initiated by IL-13. Down-regulation of Il13ra1 combined with up-regulation of Il12b (30.2-fold), suggested switch to a pro-inflammatory response by 4 hrs post H37Rv-infection. Whereas no significant change in cytokine concentration or transcription was observed during the first hour post Δ-mce1 H37Rv-infection, a significant decline of IL-1b, IL-9, IL-13, Eotaxin and GM-CSF combined with increased transcription of Il12b (25.1-fold) and Inb1 (17.9-fold) by 4 hrs, indicated a pro-inflammatory response. The balance between pro-and anti-inflammatory responses during the early stages of infection may have significant bearing on outcome.
format article
author Ruth Stavrum
Anne-Kristin Stavrum
Håvard Valvatne
Lee W Riley
Elling Ulvestad
Inge Jonassen
Jörg Assmus
T Mark Doherty
Harleen M S Grewal
author_facet Ruth Stavrum
Anne-Kristin Stavrum
Håvard Valvatne
Lee W Riley
Elling Ulvestad
Inge Jonassen
Jörg Assmus
T Mark Doherty
Harleen M S Grewal
author_sort Ruth Stavrum
title Modulation of transcriptional and inflammatory responses in murine macrophages by the Mycobacterium tuberculosis mammalian cell entry (Mce) 1 complex.
title_short Modulation of transcriptional and inflammatory responses in murine macrophages by the Mycobacterium tuberculosis mammalian cell entry (Mce) 1 complex.
title_full Modulation of transcriptional and inflammatory responses in murine macrophages by the Mycobacterium tuberculosis mammalian cell entry (Mce) 1 complex.
title_fullStr Modulation of transcriptional and inflammatory responses in murine macrophages by the Mycobacterium tuberculosis mammalian cell entry (Mce) 1 complex.
title_full_unstemmed Modulation of transcriptional and inflammatory responses in murine macrophages by the Mycobacterium tuberculosis mammalian cell entry (Mce) 1 complex.
title_sort modulation of transcriptional and inflammatory responses in murine macrophages by the mycobacterium tuberculosis mammalian cell entry (mce) 1 complex.
publisher Public Library of Science (PLoS)
publishDate 2011
url https://doaj.org/article/80895a8479bf4a1daf90a098e2e50040
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