Concerted IL-25R and IL-4Rα signaling drive innate type 2 effector immunity for optimal helminth expulsion

  1. Katherine A Smith  Is a corresponding author
  2. Stephan Löser
  3. Fumi Varyani
  4. Yvonne Harcus
  5. Henry J McSorley
  6. Andrew NJ McKenzie
  7. Rick M Maizels  Is a corresponding author
  1. Cardiff University, United Kingdom
  2. University of Cape Town, South Africa
  3. University of Glasgow, United Kingdom
  4. University of Edinburgh, United Kingdom
  5. MRC Laboratory of Molecular Biology, United Kingdom
6 figures, 1 table and 1 additional file

Figures

IL-25R signaling is required for expulsion of H.

polygyrus from BALB/c mice. H. polygyrus-infected BALB/c or Il17rb-deficient (IL25R–/–) BALB/c mice were analyzed at day 14 post-infection for fecal egg counts (A) and intestinal adult worm burden (B

https://doi.org/10.7554/eLife.38269.002
IL-25R signaling is required within the hematopoietic compartment for efficient expulsion.

Bone marrow chimeras generated from BALB/c (WT) or Il17rb-deficient (KO) donor and BALB/c (WT) or Il17rb-deficient (KO) recipient mice were infected with H. polygyrus and intestinal adult worm …

https://doi.org/10.7554/eLife.38269.003
IL-25R signaling synergises with IL-4Rα within the innate immune compartment to facilitate efficient worm expulsion.

H. polygyrus-infected Rag1-/- mice (RAG-/-) were given 0.4 µg recombinant IL-25 i.p. days 14–17 (late) post-infection with or without a complex of 5 μg rIL-4 and 25 μg anti-IL-4 (IL-4C) on days 13, …

https://doi.org/10.7554/eLife.38269.004
IL-25 induces protective immune responses in the late stage of infection.

H. polygyrus-infected C57BL/6 mice were given 0.4 μg recombinant IL-25 i.p. at day 1–4 (early) or day 14–17 (late) post-infection according to the schedule shown in (A). Before administration of …

https://doi.org/10.7554/eLife.38269.005
IL-25 drives alternative activation and IL-13 expression of macrophages.

H. polygyrus-infected C57BL/6 mice were given 0.4 μg recombinant IL-25 i.p. at day 14–17 (late) post-infection. At day 18 post-infection, PL cells were taken and stimulated with 10 μg Brefeldin A to …

https://doi.org/10.7554/eLife.38269.006
IL-4Rα expression is required for activation of the immune system by IL-25.

H. polygyrus-infected Il4ra-/- mice (IL-4R-/-) were given 0.4 μg recombinant IL-25 i.p. days 14–17 (late) post-infection (A). Mice were analyzed at day 28 post-infection for intestinal adult worm …

https://doi.org/10.7554/eLife.38269.007

Tables

Key resources table
Reagent type
(species) or
resource
DesignationSource or referenceIdentifiers
Mus musculus,
BALB/c
Il17rb-/- (IL-25R-/-)Neill et al. (2010)
Nuocytes represent a new innate
effector leukocyte that mediates
type-2 immunity. Nature
464:1367–1370
Mus musculus,
C57BL/6
Rag1-/-Mombaerts,P., Iacomini,J.,
Johnson, R.S., Herrup, K.,
Tonegawa,S., and Papaioannou, V. E.
1992. Cell. Vol 68: 869–877.
PMID: 1547488
Mus musculus,
C57BL/6
Il4ra-/-Noben-Trauth N, Shultz LD,
Brombacher F, Urban
JF, Jr., Gu H, Paul WE. 1997.
An interleukin 4 (IL-4)-independent
pathway for CD4 + T cell IL-4 production
is revealed in IL-4 receptor-deficient
mice. Proc Natl Acad Sci
USA 94:10838–10843.
ParasiteHeligmosomoides
polygyrus bakeri
Johnston et al., 2015.
Cultivation of Heligmosomoides
polygyrus: an immunomodulatory
nematode parasite and its
secreted products. Journal
of Visualized Experiments
98:e52412.
AntibodyAnti-IL-4BioXCellClone 11B11
AntibodyAnti-IL-13BioLegendJES10-5A2
AntibodyAnti-CD90.2BioXCell30H12
AntibodyAnti-SiglecFBD PharmingenE50-2440
AntibodyAnti-CD11bBioLegendM1/70
AntibodyAnti-F4/80BioLegendBM8
AntibodyAnti-Ly6GBioLegend1A8
AntibodyAnti-Ly6CBioLegendAL-21
AntibodyAnti-RELMαR and D Systems22603
AntibodyAnti-Arginase-1
(Polyclonal)
R and D SystemsIC5868P
AntibodyAnti-LineageBioLegend17A2,RB6-8C5,RA3-6B2,Ter-119,M1/70
Peptide,
recombinant protein
IL-4Peprotech214–14
Peptide,
recombinant protein
IL-25BioLegend587302
Commercial
assay or kit
Foxp3 Staining KiteBioScience88–8118
OtherControl IgG2b
immunoglobulin
BioXcellLTF-2
OtherAnti-CD90.2
Microbeads
Miltenyi130-049-101

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