Suppression of OVA-alum induced allergy by Heligmosomoides polygyrus products is MyD88-, TRIF-, regulatory T- and B cell-independent, but is associated with reduced innate lymphoid cell activation.
The murine intestinal nematode Heligmosomoides polygyrus exerts multiple immunomodulatory effects in the host, including the suppression of allergic inflammation in mice sensitized to allergen presented with alum adjuvant. Similar suppression is attained by co-administration of H. polygyrus excretory/secretory products (HES) with the sensitizing dose of ovalbumin (OVA) in alum. We investigated the mechanism of suppression by HES in this model, and found it was maintained in MyD88xTRIF-deficient mice, implying no role for helminth- or host-derived TLR ligands, or IL-1 family cytokines that signal in a MyD88- or TRIF-dependent manner. We also found suppression was unchanged in µMT mice, which lack B2 B cells, and that suppression was not abrogated when regulatory T cells were depleted in Foxp3.LuciDTR-4 mice. However, reduced IL-5 production was seen in the first 12 h after injection of OVA-alum when HES was co-administered, associated with reduced activation of IL-5(+) and IL-13(+) group 2 innate lymphoid cells. Thus, the suppressive effects of HES on alum-mediated OVA sensitization are reflected in the very earliest innate response to allergen exposure in vivo.
Institute of Immunology and Infection Research, and Centre for Immunity, Infection and Evolution, School of Biological Sciences, Ashworth Laboratories, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK; Centre for Inflammation Research, University of Edinburgh, Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh EH16 4TJ, UK. Electronic address: hmcsorle@staffmail.ed.ac.uk.
Henry J
HJ
McSorley
Institute of Immunology and Infection Research, and Centre for Immunity, Infection and Evolution, School of Biological Sciences, Ashworth Laboratories, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK.
Natalie F
NF
Blair
Institute of Immunology and Infection Research, and Centre for Immunity, Infection and Evolution, School of Biological Sciences, Ashworth Laboratories, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK.
Elaine
E
Robertson
Institute of Immunology and Infection Research, and Centre for Immunity, Infection and Evolution, School of Biological Sciences, Ashworth Laboratories, University of Edinburgh, West Mains Road, Edinburgh EH9 3JT, UK.
Rick M
RM
Maizels
D033942:Adaptor Proteins, Vesicular Transport / Q000172:deficiency / Q000276:immunology; D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000534:Alum Compounds / Q000008:administration & dosage; D000818:Animals; D060151:B-Lymphocytes, Regulatory / Q000276:immunology; D006967:Hypersensitivity / Q000276:immunology*; D007153:Immunologic Deficiency Syndromes / Q000276:immunology; D008214:Lymphocytes / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009351:Nematospiroides dubius / Q000276:immunology*; D010047:Ovalbumin / Q000008:administration & dosage; D000081207:Primary Immunodeficiency Diseases; D015398:Signal Transduction / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D033942:Adaptor Proteins, Vesicular Transport; D000276:Adjuvants, Immunologic; D000534:Alum Compounds; D010047:Ovalbumin; C476286:Ticam1 protein, mouse; C041524:aluminum sulfate
Allergy; Alum; Asthma; HES; Heligmosomoides polygyrus