IL-4Rα-Dependent Alternative Activation of Macrophages Is Not Decisive for Mycobacterium tuberculosis Pathology and Bacterial Burden in Mice

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dc.contributor.authorGuler, Retoen_ZA
dc.contributor.authorParihar, Suraj Pen_ZA
dc.contributor.authorSavvi, Suzanaen_ZA
dc.contributor.authorLogan, Erinen_ZA
dc.contributor.authorSchwegmann, Anitaen_ZA
dc.contributor.authorRoy, Sugataen_ZA
dc.contributor.authorNieuwenhuizen, Natalie Een_ZA
dc.contributor.authorOzturk, Muminen_ZA
dc.contributor.authorSchmeier, Sebastianen_ZA
dc.contributor.authorSuzuki, Harukazuen_ZA
dc.contributor.authorBrombacher, Franken_ZA
dc.date.accessioned2016-01-11T06:54:43Z
dc.date.available2016-01-11T06:54:43Z
dc.date.issued2015en_ZA
dc.description.abstractClassical activation of macrophages (caMph or M1) is crucial for host protection against Mycobacterium tuberculosis ( Mtb ) infection. Evidence suggests that IL-4/IL-13 alternatively activated macrophages (aaMph or M2) are exploited by Mtb to divert microbicidal functions of caMph. To define the functions of M2 macrophages during tuberculosis (TB), we infected mice deficient for IL-4 receptor α on macrophages (LysM cre IL-4Rα -/lox ) with Mtb . We show that absence of IL-4Rα on macrophages does not play a major role during infection with Mtb H37Rv, or the clinical Beijing strain HN878. This was demonstrated by similar mortality, bacterial burden, histopathology and T cell proliferation between infected wild-type (WT) and LysM cre IL-4Rα -/lox mice. Interestingly, we observed no differences in the lung expression of inducible nitric oxide synthase (iNOS) and Arginase 1 (Arg1), well-established markers for M1/M2 macrophages among the Mtb -infected groups. Kinetic expression studies of IL-4/IL-13 activated bone marrow-derived macrophages (BMDM) infected with HN878, followed by gene set enrichment analysis, revealed that the MyD88 and IL-6, IL-10, G-CSF pathways are significantly enriched, but not the IL-4Rα driven pathway. Together, these results suggest that IL-4Rα-macrophages do not play a central role in TB disease progression.en_ZA
dc.identifier.apacitationGuler, R., Parihar, S. P., Savvi, S., Logan, E., Schwegmann, A., Roy, S., ... Brombacher, F. (2015). IL-4Rα-Dependent Alternative Activation of Macrophages Is Not Decisive for Mycobacterium tuberculosis Pathology and Bacterial Burden in Mice. <i>PLoS One</i>, http://hdl.handle.net/11427/16290en_ZA
dc.identifier.chicagocitationGuler, Reto, Suraj P Parihar, Suzana Savvi, Erin Logan, Anita Schwegmann, Sugata Roy, Natalie E Nieuwenhuizen, et al "IL-4Rα-Dependent Alternative Activation of Macrophages Is Not Decisive for Mycobacterium tuberculosis Pathology and Bacterial Burden in Mice." <i>PLoS One</i> (2015) http://hdl.handle.net/11427/16290en_ZA
dc.identifier.citationGuler, R., Parihar, S. P., Savvi, S., Logan, E., Schwegmann, A., Roy, S., ... & Brombacher, F. (2015). IL-4Rα-Dependent Alternative Activation of Macrophages Is Not Decisive for Mycobacterium tuberculosis Pathology and Bacterial Burden in Mice. PloS one, 10(3), e0121070. doi:10.1371/journal.pone.0121070en_ZA
dc.identifier.ris TY - Journal Article AU - Guler, Reto AU - Parihar, Suraj P AU - Savvi, Suzana AU - Logan, Erin AU - Schwegmann, Anita AU - Roy, Sugata AU - Nieuwenhuizen, Natalie E AU - Ozturk, Mumin AU - Schmeier, Sebastian AU - Suzuki, Harukazu AU - Brombacher, Frank AB - Classical activation of macrophages (caMph or M1) is crucial for host protection against Mycobacterium tuberculosis ( Mtb ) infection. Evidence suggests that IL-4/IL-13 alternatively activated macrophages (aaMph or M2) are exploited by Mtb to divert microbicidal functions of caMph. To define the functions of M2 macrophages during tuberculosis (TB), we infected mice deficient for IL-4 receptor α on macrophages (LysM cre IL-4Rα -/lox ) with Mtb . We show that absence of IL-4Rα on macrophages does not play a major role during infection with Mtb H37Rv, or the clinical Beijing strain HN878. This was demonstrated by similar mortality, bacterial burden, histopathology and T cell proliferation between infected wild-type (WT) and LysM cre IL-4Rα -/lox mice. Interestingly, we observed no differences in the lung expression of inducible nitric oxide synthase (iNOS) and Arginase 1 (Arg1), well-established markers for M1/M2 macrophages among the Mtb -infected groups. Kinetic expression studies of IL-4/IL-13 activated bone marrow-derived macrophages (BMDM) infected with HN878, followed by gene set enrichment analysis, revealed that the MyD88 and IL-6, IL-10, G-CSF pathways are significantly enriched, but not the IL-4Rα driven pathway. Together, these results suggest that IL-4Rα-macrophages do not play a central role in TB disease progression. DA - 2015 DB - OpenUCT DO - 10.1371/journal.pone.0121070 DP - University of Cape Town J1 - PLoS One LK - https://open.uct.ac.za PB - University of Cape Town PY - 2015 T1 - IL-4Rα-Dependent Alternative Activation of Macrophages Is Not Decisive for Mycobacterium tuberculosis Pathology and Bacterial Burden in Mice TI - IL-4Rα-Dependent Alternative Activation of Macrophages Is Not Decisive for Mycobacterium tuberculosis Pathology and Bacterial Burden in Mice UR - http://hdl.handle.net/11427/16290 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/16290
dc.identifier.urihttp://dx.doi.org/10.1371/journal.pone.0121070
dc.identifier.vancouvercitationGuler R, Parihar SP, Savvi S, Logan E, Schwegmann A, Roy S, et al. IL-4Rα-Dependent Alternative Activation of Macrophages Is Not Decisive for Mycobacterium tuberculosis Pathology and Bacterial Burden in Mice. PLoS One. 2015; http://hdl.handle.net/11427/16290.en_ZA
dc.language.isoengen_ZA
dc.publisherPublic Library of Scienceen_ZA
dc.publisher.departmentDivision of Immunologyen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rightsThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_ZA
dc.rights.holder© 2015 Guler et alen_ZA
dc.rights.urihttp://creativecommons.org/licenses/by/4.0en_ZA
dc.sourcePLoS Oneen_ZA
dc.source.urihttp://journals.plos.org/plosoneen_ZA
dc.subject.otherMacrophagesen_ZA
dc.subject.otherMycobacterium tuberculosisen_ZA
dc.subject.otherT cellsen_ZA
dc.subject.otherHistopathologyen_ZA
dc.subject.otherAlveolar macrophagesen_ZA
dc.subject.otherSpleenen_ZA
dc.subject.otherTuberculosisen_ZA
dc.subject.otherMycobacterium bovisen_ZA
dc.titleIL-4Rα-Dependent Alternative Activation of Macrophages Is Not Decisive for Mycobacterium tuberculosis Pathology and Bacterial Burden in Miceen_ZA
dc.typeJournal Articleen_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceArticleen_ZA
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