title: IL-4Rα-dependent alternative activation of macrophages is not decisive for Mycobacterium tuberculosis pathology and bacterial burden in mice.
abstract: 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.
authors: International Centre for Genetic Engineering & Biotechnology (ICGEB), Cape Town component and Institute of Infectious Diseases and Molecular Medicine (IDM), Division of Immunology, University of Cape Town, Cape Town, South Africa.
authors: Reto
authors: R
authors: Guler
authors: International Centre for Genetic Engineering & Biotechnology (ICGEB), Cape Town component and Institute of Infectious Diseases and Molecular Medicine (IDM), Division of Immunology, University of Cape Town, Cape Town, South Africa.
authors: Suraj P
authors: SP
authors: Parihar
authors: International Centre for Genetic Engineering & Biotechnology (ICGEB), Cape Town component and Institute of Infectious Diseases and Molecular Medicine (IDM), Division of Immunology, University of Cape Town, Cape Town, South Africa.
authors: Suzana
authors: S
authors: Savvi
authors: International Centre for Genetic Engineering & Biotechnology (ICGEB), Cape Town component and Institute of Infectious Diseases and Molecular Medicine (IDM), Division of Immunology, University of Cape Town, Cape Town, South Africa.
authors: Erin
authors: E
authors: Logan
authors: International Centre for Genetic Engineering & Biotechnology (ICGEB), Cape Town component and Institute of Infectious Diseases and Molecular Medicine (IDM), Division of Immunology, University of Cape Town, Cape Town, South Africa.
authors: Anita
authors: A
authors: Schwegmann
authors: RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama, Japan.
authors: Sugata
authors: S
authors: Roy
authors: International Centre for Genetic Engineering & Biotechnology (ICGEB), Cape Town component and Institute of Infectious Diseases and Molecular Medicine (IDM), Division of Immunology, University of Cape Town, Cape Town, South Africa.
authors: Natalie E
authors: NE
authors: Nieuwenhuizen
authors: International Centre for Genetic Engineering & Biotechnology (ICGEB), Cape Town component and Institute of Infectious Diseases and Molecular Medicine (IDM), Division of Immunology, University of Cape Town, Cape Town, South Africa.
authors: Mumin
authors: M
authors: Ozturk
authors: Massey University, Institute of Natural and Mathematical Sciences, Auckland, New Zealand.
authors: Sebastian
authors: S
authors: Schmeier
authors: RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama, Japan.
authors: Harukazu
authors: H
authors: Suzuki
authors: International Centre for Genetic Engineering & Biotechnology (ICGEB), Cape Town component and Institute of Infectious Diseases and Molecular Medicine (IDM), Division of Immunology, University of Cape Town, Cape Town, South Africa.
authors: Frank
authors: F
authors: Brombacher
mesh_terms: D000818:Animals; D001119:Arginase / Q000096:biosynthesis / Q000378:metabolism; D058491:Bacterial Load; D049109:Cell Proliferation; D018450:Disease Progression; D015971:Gene Expression Regulation, Enzymologic; D053662:Interleukin-4 Receptor alpha Subunit / Q000276:immunology*; D008262:Macrophage Activation; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000502:physiology*; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D011650:Pulmonary Alveoli / Q000276:immunology / Q000382:microbiology; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014397:Tuberculosis, Pulmonary / Q000276:immunology / Q000382:microbiology* / Q000473:pathology*
chemical_list: D053662:Interleukin-4 Receptor alpha Subunit; D053594:Myeloid Differentiation Factor 88; D052247:Nitric Oxide Synthase Type II; C544448:Arg1 protein, mouse; D001119:Arginase