Protective immunity against intestinal helminths requires induction of robust Type-2 immunity orchestrated by various cellular and soluble effectors which promote goblet cell hyperplasia, mucus production, epithelial proliferation and smooth muscle contractions to expel worms and reestablish immune homeostasis. Conversely, defects in type-2 immunity result in ineffective helminth clearance, persistent infection and chronic inflammation. We identify A20 as an essential myeloid factor for the induction of type-2 immune responses against the intestinal parasite Trichuris muris. Myeloid cell-specific loss of A20 in mice (A20 myel-KO deficient mice are not able to induce anti-helmith type-2 immune responses while instead mount detrimental Th1/Th17 polarized immune responses. Antibody-mediated neutralization of the type-1 cytokines IFNγ, IL18 and IL12 prevents Th1/Th17 polarization and reestablishes Type-2 mediated protective immunity against Trichuris muris in A20 myel-KO mice. In contrast, the strong Th1/Th17 biased immunity in A20 myel-KO mice offers protection against Salmonella infection. We hereby identify A20 as an essential myeloid factor to initiate approriate adaptive immunity in response to infection, and to induce a balanced type-2 immune response against the intestinal parasite Trichuris muris.) results in chronic Trichuris muris infection and intestinal inflammation. Myeloid A20 Graphical abstract: The clearance of gastrointestinal helmiths depends on type-2 immunity. Helminths interact with and damage intestinal tissue, which leads to the release of intracellular DAMPs and cytokines such as TSLP and IL33, and IL25 produced by epithelial cells. These factors may activate myeloid cells and ILC’s, which further activate T and B cells to mount effective Th2 responses and the secretion of IL4, IL5 and IL13 cytokines, as well as helminth-specific IgG1 immunoglobulins, leading to effective expulsion of the helminths. Deletion of A20 in the myeloid cells leads to enhanced secretion of type-1 cytokines, including IL12, IL18 and IFNγ, which impede type-2 immune-mediated helminth clearance and promotes chronic intestinal inflammation.
In this repository you can find all the code used for the Bulk RNA-seq data analysis. Below you can find an overview:
- 1.Script_DESeq2_Pre_processing.R: Allows you to get the original DESeq2 Object used for all the analysis.
- 2.Script_Functions.R: Contains all functions used for the analysis.
- 3.Script_Figure_1_E_F_G_H_I_J_K_L.R: Script used for generating Figure 1 (E,F,G,H,I,J,K,L) & Supplementary Figure 2 (E,F) & Supplementary Figure 4C.
- 4.Script_Figure_4.R: Script used for generating Figure 4.
- 5.session_info.txt: Contains all packages used and their respective versions for the analysis.
Notes:
- To be able to run the provided R scripts you need the raw_counts.csv file provided on GEOXXXXXX and additional files found in the data folder.
Manuscript: 
