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The parasite Cryptosporidia infects and completes its entire life cycle within the intestinal epithelium. It has been long appreciated that interferon gamma is critical for protection, but the source of this cytokine, the mechanism of induction and the cell site of action have been unknown. Here Gullicksrud et al.1 demonstrate in a mouse model that interferon gamma regulation and protection center on the infected epithelial cell. The work is of importance for the fundamental advances it provides on mucosal defense from intracellular parasitism, as well as providing a foundation for the advancement of vaccination against this cause of diarrhea, malnutrition and death of infants in low and middle income countries.
Recent findings by Felton et al. and Qiu et al. unveil the importance of the transcription factor Aiolos for tissue-resident eosinophils and group 2 innate lymphoid cells (ILC2s). The authors find that Aiolos regulates the transcriptomic profile and chromatin landscape, both of which are essential for eosinophil and ILC2 localisation in tissues, as well as their function. These studies place Aiolos as a molecular guardian that regulates tissue-resident type 2 innate cells.
The interaction between fungal pathogens and host epithelial barriers remains largely unexplored. In a recent issue of Nature Microbiology, Pekmezovic et al. (Nat. Microbiol. 2021) provides evidence for the pivotal role of mitochondria-associated type I interferon signalling in the pathophysiology of vulvovaginal candidiasis.
Type 1 Innate lymphoid cells (ILC1) accumulate in the inflamed mucosa of patients with Crohn’s disease (CD) but their role in CD pathogenesis remains poorly known. In a recent issue of Nature materials, Jowett et al. (Nat. Mat. 2020) used a coculture model with intestinal organoids to show that ILC1 could promote intestinal epithelial growth and tissue remodeling through an unexpected mechanism that involves the transforming growth factor 1 (TGF-β1) and the metalloproteinase MMP9.
A recent paper in Cell proposes a new role for macrophages in the distal colonic mucosa, namely the generation of balloon-like processes (BLPs) that sample luminal contents and protect epithelial cells from the toxic effects of fungal metabolites absorbed during this process. Here Allan Mowat and Calum Bain discuss the implications of these novel findings for intestinal physiology and macrophage biology, highlighting how they extend our understanding of how tissue resident macrophages can adapt precisely to the physiological needs of individual anatomical niches.
