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. 2021 Dec 20;15(2):257–267. doi: 10.1038/s41385-021-00473-9

Fig. 6. H. polygyrus-specific footpad swelling and muted skin IFNγ responses to mycobacterial antigens persist after removal of worms.

Fig. 6

Mice were infected with H. polygyrus (Hp) or not (-) and some dewormed (Dw) 4 weeks later. a Footpad swelling after soluble worm antigen (SWAg) from H. polygyrus injection in the footpad 12 weeks post infection. or 10 weeks after deworming. b shows the setup for c and d Mice were dewormed 4 weeks after Hp infection and 10 weeks later whole cell lysate (WCL) from M. tuberculosis was injected in the left ear and the right ear was left untreated. Four weeks later, ears were collected, and ear cells co-cultured with BMDCs expressing WCL overnight and analysed by flow cytometry. cd Frequency of IFN-γ+ cells out of CD4+ T cells. ad One out of at least two independent experiments with similar results are shown. Each dot represents the mean ± SEM of a group of mice (n ≥ 4 per group) in line graphs or an individual mouse in bar graphs, where bars indicate mean ± SEM. Statistical differences were analysed by unpaired t-tests (a, c) or Mann–Whitney U test (d) and depicted as *p < 0.05, **p < 0.01, ****p < 0.0001 or in a as above for 12 weeks Hp infected mice and as #p < 0.05, ####p < 0.0001 for mice dewormed 10 weeks prior to SWAg injection. e shows a graphical summary of a suggested model for our findings. Upper panel: Intestinal H. polygyrus infection primes worm-specific CD4+ T cells into CCR4 and CCR10-expressing TH2 cells in the mesLNs. Primed cells travel through the circulation to the skin where they remain after the infection is cleared and total numbers have normalised, persistently transforming the skin CD4+ T cell pool. Lower panel: Intradermal WCL injection causes mycobacteria-reactive TH1 cells to accumulate in the skin. The increased levels of TH2 cytokines present in the skin of worm infected or worm-cleared mice dampen the functionality of TH1 cells, muting their capacity to produce IFN-γ in response to restimulation with mycobacterial products.

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