Dr. Wiebke Hartmann (Hamburg / DE), Lennart Heepmann (Hamburg / DE), Dr. rer nat Lara Linnemann (Hamburg / DE), Prof Paula Lincona Limon (Mexico City / MX), Prof. Dr. Minka Breloer (Hamburg / DE)
Abstract text
Introduction: During their migration helminths induce the release of tissue-derived alarmins such as IL-33 which promote the initiation of a protective type 2 immune response. We have previously demonstrated that mucosal mast cells are central for the timely ejection of Strongyloides ratti from the intestine of Infected mice. Application of recombinant IL-33 or enhancement of endogenous IL-33 accelerated the degranulation of mucosal mast cell in an IL-9 dependent manner, resulting in rapid expulsion of the S. ratti.
Objective: Aim of the study was to identify the cellular sources of IL-9 in S. ratti infected mice.
Material and Methods: BALB/c IL-9 GFP Reporter mice were used to analyze IL-9 expressing cells in 4 different groups: naïve, IL-33 treated, IL-33 treated + S. ratti infected and S. ratti infected mice. Lung, mesenteric lymph nodes (mLN) and lamina propria-derived cells were isolated at day 2, 6 and 10 p.i. Frequencies of granulocytes, mast cells, B cells, NK cells, various T cell (CD4, CD8, gd T cells) and innate lymphoid cell (ILC) subsets were analyzed in several organs and their expression of the pluripotent cytokine IL-9 was quantified by flow cytometry.
Results: Kinetic analysis revealed a pronounced expansion and expression of IL-9 GFP by ILC subsets such as ILC2 and NK cells in lung and mLN cells of IL-33 treated mice, as expected. ILC2s were identified as the main IL-9 expressing cell type in the lung of all 3 groups compared to naïve mice. Strikingly, the expansion of these cell types was not visible in the lung and mLN of S. ratti infected mice and was not altered by additional IL-33 treatment. In the small intestine (lamina propria) we observed a late expression of IL-9 by GATA-3+ CD4+ T cells and mast cells at day 10 p.i. in S. ratti infected mice. Expression of IL-9 by these cells was already detectable at day 6 p.i. in IL-33 treated + S. ratti infected mice and was absent in IL-33 treated mice indicating a S. ratti-specific expression of IL-9 at the site of infection.
Conclusion: Artificial activation of innate cells by application of the alarmin cytokine IL-33 induces a rapid and pronounced expression of IL-9 by ILC subsets. By contrast, simultaneous infection with S. ratti dampened the expansion of ILC subsets indicating counter regulation of IL-33 induced anti-helminth immune response.