IL-33 delivery induces serous cavity macrophage proliferation independent of interleukin-4 receptor alpha.
IL-33 plays an important role in the initiation of type-2 immune responses, as well as the enhancement of type 2 effector functions. Engagement of the IL-33 receptor on macrophages facilitates polarization to an alternative activation state by amplifying IL-4 and IL-13 signaling to IL-4Rα. IL-4 and IL-13 also induce macrophage proliferation but IL-33 involvement in this process has not been rigorously evaluated. As expected, in vivo delivery of IL-33 induced IL-4Rα-dependent alternative macrophage activation in the serous cavities. IL-33 delivery also induced macrophages to proliferate but, unexpectedly, this was independent of IL-4Rα signaling. In a filarial nematode infection model in which IL-4Rα-dependent alternative activation and proliferation in the pleural cavity is well described, IL-33R was essential for alternative activation but not macrophage proliferation. Similarly, during Alternaria alternata induced airway inflammation, which provokes strong IL-33 responses, we observed that both IL-4Rα and IL-33R were required for alternative activation, while macrophage proliferation in the pleural cavity was still evident in the absence of either receptor alone. Our data show that IL-33R and IL-4Rα promote macrophage proliferation independently of each other, but both are essential for induction of alternative activation.
School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3FL, UK.|Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, EH16 4TJ, UK.
Lucy H
LH
Jackson-Jones
School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3FL, UK.|Faculty of Biology, Medicine & Health, University of Manchester, Manchester, M13 9PT, UK.
Dominik
D
Rückerl
Faculty of Biology, Medicine & Health, University of Manchester, Manchester, M13 9PT, UK.
Freya
F
Svedberg
School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3FL, UK.
Sheelagh
S
Duncan
Institute of Infection, Immunity & Inflammation, University of Glasgow, Glasgow, G12 8TA, UK.
Rick M
RM
Maizels
School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3FL, UK.|Faculty of Biology, Medicine & Health, University of Manchester, Manchester, M13 9PT, UK.
Tara E
TE
Sutherland
Centre for Inflammation Research, University of Edinburgh, Edinburgh, EH16 4TJ, UK.
Stephen J
SJ
Jenkins
School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3FL, UK.|Centre for Inflammation Research, University of Edinburgh, Edinburgh, EH16 4TJ, UK.
Henry J
HJ
McSorley
Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, EH16 4TJ, UK.
Cécile
C
Bénézech
Faculty of Biology, Medicine & Health, University of Manchester, Manchester, M13 9PT, UK.
Andrew S
AS
MacDonald
School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3FL, UK. judi.allen@manchester.ac.uk.|Faculty of Biology, Medicine & Health, University of Manchester, Manchester, M13 9PT, UK. judi.allen@manchester.ac.uk.
Judith E
JE
Allen
D000528:Alternaria / Q000276:immunology*; D060487:Alternariosis / Q000276:immunology*; D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D005368:Filariasis / Q000276:immunology*; D005370:Filarioidea / Q000276:immunology; D000072179:Interleukin-1 Receptor-Like 1 Protein / Q000235:genetics / Q000378:metabolism*; D000067596:Interleukin-33 / Q000378:metabolism*; D008262:Macrophage Activation; D008264:Macrophages / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D035422:Pleural Cavity / Q000473:pathology; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012704:Serous Membrane / Q000276:immunology*; D015398:Signal Transduction; D053662:Interleukin-4 Receptor alpha Subunit
D000072179:Interleukin-1 Receptor-Like 1 Protein; D000067596:Interleukin-33; D011956:Receptors, Cell Surface; C504002:Il4ra protein, mouse; D053662:Interleukin-4 Receptor alpha Subunit
Alternaria; IL-33; IL-4; Macrophage; Nematode; Proliferation