Concerted IL-25R and IL-4Rα signaling drive innate type 2 effector immunity for optimal helminth expulsion
- Cardiff University, United Kingdom
- University of Cape Town, South Africa
- University of Glasgow, United Kingdom
- University of Edinburgh, United Kingdom
- MRC Laboratory of Molecular Biology, United Kingdom
Figures
Figure 1
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…
Figure 2
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 …
Figure 3
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, …
Figure 4
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 …
Figure 5
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 …
Figure 6
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 …
Tables
Key resources table
| Reagent type (species) or resource | Designation | Source or reference | Identifiers |
|---|---|---|---|
| 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. | |
| Parasite | Heligmosomoides polygyrus bakeri | Johnston et al., 2015. Cultivation of Heligmosomoides polygyrus: an immunomodulatory nematode parasite and its secreted products. Journal of Visualized Experiments 98:e52412. | |
| Antibody | Anti-IL-4 | BioXCell | Clone 11B11 |
| Antibody | Anti-IL-13 | BioLegend | JES10-5A2 |
| Antibody | Anti-CD90.2 | BioXCell | 30H12 |
| Antibody | Anti-SiglecF | BD Pharmingen | E50-2440 |
| Antibody | Anti-CD11b | BioLegend | M1/70 |
| Antibody | Anti-F4/80 | BioLegend | BM8 |
| Antibody | Anti-Ly6G | BioLegend | 1A8 |
| Antibody | Anti-Ly6C | BioLegend | AL-21 |
| Antibody | Anti-RELMα | R and D Systems | 22603 |
| Antibody | Anti-Arginase-1 (Polyclonal) | R and D Systems | IC5868P |
| Antibody | Anti-Lineage | BioLegend | 17A2,RB6-8C5,RA3-6B2,Ter-119,M1/70 |
| Peptide, recombinant protein | IL-4 | Peprotech | 214–14 |
| Peptide, recombinant protein | IL-25 | BioLegend | 587302 |
| Commercial assay or kit | Foxp3 Staining Kit | eBioScience | 88–8118 |
| Other | Control IgG2b immunoglobulin | BioXcell | LTF-2 |
| Other | Anti-CD90.2 Microbeads | Miltenyi | 130-049-101 |
Additional files
-
Transparent reporting form
- https://doi.org/10.7554/eLife.38269.008
