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

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 funct...

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Main Authors:	Guler, Reto, Parihar, Suraj P., Savvi, Suzana, Logan, Erin, Schwegmann, Anita, Roy, Sugata, Nieuwenhuizen, Natalie E., Ozturk, Mumin, Schmeier, Sebastian, Suzuki, Harukazu, Brombacher, Frank
Format:	Online
Language:	English
Published:	Public Library of Science 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366092/

id	pubmed-4366092
recordtype	oai_dc
spelling	pubmed-43660922015-03-23 IL-4Rα-Dependent Alternative Activation of Macrophages Is Not Decisive for Mycobacterium tuberculosis Pathology and Bacterial Burden in Mice Guler, Reto Parihar, Suraj P. Savvi, Suzana Logan, Erin Schwegmann, Anita Roy, Sugata Nieuwenhuizen, Natalie E. Ozturk, Mumin Schmeier, Sebastian Suzuki, Harukazu Brombacher, Frank Research Article 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 (LysMcreIL-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 LysMcreIL-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. Public Library of Science 2015-03-19 /pmc/articles/PMC4366092/ /pubmed/25790379 http://dx.doi.org/10.1371/journal.pone.0121070 Text en © 2015 Guler et al http://creativecommons.org/licenses/by/4.0/ This 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 properly credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Guler, Reto Parihar, Suraj P. Savvi, Suzana Logan, Erin Schwegmann, Anita Roy, Sugata Nieuwenhuizen, Natalie E. Ozturk, Mumin Schmeier, Sebastian Suzuki, Harukazu Brombacher, Frank
spellingShingle	Guler, Reto Parihar, Suraj P. Savvi, Suzana Logan, Erin Schwegmann, Anita Roy, Sugata Nieuwenhuizen, Natalie E. Ozturk, Mumin Schmeier, Sebastian Suzuki, Harukazu Brombacher, Frank IL-4Rα-Dependent Alternative Activation of Macrophages Is Not Decisive for Mycobacterium tuberculosis Pathology and Bacterial Burden in Mice
author_facet	Guler, Reto Parihar, Suraj P. Savvi, Suzana Logan, Erin Schwegmann, Anita Roy, Sugata Nieuwenhuizen, Natalie E. Ozturk, Mumin Schmeier, Sebastian Suzuki, Harukazu Brombacher, Frank
author_sort	Guler, Reto
title	IL-4Rα-Dependent Alternative Activation of Macrophages Is Not Decisive for Mycobacterium tuberculosis Pathology and Bacterial Burden in Mice
title_short	IL-4Rα-Dependent Alternative Activation of Macrophages Is Not Decisive for Mycobacterium tuberculosis Pathology and Bacterial Burden in Mice
title_full	IL-4Rα-Dependent Alternative Activation of Macrophages Is Not Decisive for Mycobacterium tuberculosis Pathology and Bacterial Burden in Mice
title_fullStr	IL-4Rα-Dependent Alternative Activation of Macrophages Is Not Decisive for Mycobacterium tuberculosis Pathology and Bacterial Burden in Mice
title_full_unstemmed	IL-4Rα-Dependent Alternative Activation of Macrophages Is Not Decisive for Mycobacterium tuberculosis Pathology and Bacterial Burden in Mice
title_sort	il-4rα-dependent alternative activation of macrophages is not decisive for mycobacterium tuberculosis pathology and bacterial burden in mice
description	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 (LysMcreIL-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 LysMcreIL-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.
publisher	Public Library of Science
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366092/
_version_	1613200893467951104

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

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