IL-4Rα-dependent alternative activation of macrophages is not decisive for Mycobacterium tuberculosis pathology and bacterial burden in mice

PloS One
Reto GulerFrank Brombacher

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 re...Continue Reading

References

Apr 8, 1999·Clinical and Experimental Immunology·A D Howard, B S Zwilling
Jan 6, 2000·Transgenic Research·B E ClausenI Förster
Jan 4, 2003·Nature Reviews. Immunology·Siamon Gordon
Sep 10, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mercedes Gonzalez-JuarreroIan M Orme
Jun 10, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anne-Laure PauleauPeter J Murray
Oct 4, 2005·Proceedings of the National Academy of Sciences of the United States of America·Aravind SubramanianJill P Mesirov
Jan 6, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Christoph HölscherFrank Brombacher
Feb 16, 2006·European Journal of Immunology·Antje KahnertStefan H E Kaufmann
Apr 28, 2006·Nature Genetics·Michael ReichJill P Mesirov
Aug 7, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Andrea J WolfJoel D Ernst
Oct 5, 2007·Proceedings of the National Academy of Sciences of the United States of America·Anita SchwegmannFrank Brombacher
Sep 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Marie BenoitJean-Louis Mege
Oct 4, 2008·Nucleic Acids Research·Carl F SchaeferKenneth H Buetow
Dec 25, 2008·Annual Review of Immunology·Fernando O MartinezSiamon Gordon
May 27, 2010·PLoS Neglected Tropical Diseases·Benjamin G DewalsFrank Brombacher
Nov 13, 2010·Nucleic Acids Research·Ethan G CeramiChris Sander
Nov 19, 2011·Trends in Immunology·David M LoweAdrian R Martineau
May 4, 2012·The Journal of Allergy and Clinical Immunology·Natalie E NieuwenhuizenFrank Brombacher
Jul 26, 2012·FEMS Immunology and Medical Microbiology·Ana P PessanhaLilian O Moreira
Mar 23, 2013·Annual Review of Immunology·Anne O'GarraMatthew P R Berry
Mar 4, 2014·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Senait AshenafiSusanna Brighenti

❮ Previous
Next ❯

Citations

Mar 16, 2016·Mediators of Inflammation·Christoph HölscherThorsten Thye
Oct 23, 2015·Seminars in Immunopathology·Joseph E Qualls, Peter J Murray
Oct 25, 2017·Epigenetics & Chromatin·Elena DenisenkoSebastian Schmeier
Sep 18, 2015·Oncotarget·Reto GulerFrank Brombacher
Dec 14, 2018·Mucosal Immunology·Reto GulerFrank Brombacher
Nov 24, 2019·Molecular Biotechnology·Madhavan OmanakuttanDavid McMurray
Jul 6, 2021·Frontiers in Immunology·Suraj P PariharFrank Brombacher

❮ Previous
Next ❯

Methods Mentioned

BETA
FACS
flow cytometry
chips
chip

Software Mentioned

Illumina BeadScan
BeadStudio
GenePattern
FlowJo
TreeStar
GSEA

Related Concepts

Related Feeds

Aminoglycosides

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.

Aminoglycosides (ASM)

Aminoglycoside is a medicinal and bacteriologic category of traditional Gram-negative antibacterial medications that inhibit protein synthesis and contain as a portion of the molecule an amino-modified glycoside. Discover the latest research on aminoglycoside here.