Abstract
Gut innate immune defenses control bacterial populations and protect the host interior from invasion. Although excess intestinal immune activity frequently promotes inflammatory illnesses, we know little about the consequences of chronic innate immune activity exclusively in endodermal gut cells of an otherwise normal animal. To address this question, we examined the consequences of persistent inflammatory signals in adult fly intestinal progenitor cells. We found that constitutive immune activity disrupts expression of homeostatic regulators such as Notch pathway components and induces hyperplasia throughout the gut. Consistent with these observations, we found that persistent immune signals interfere with progenitor cell differentiation and exacerbate the formation of Notch-dependent intestinal tumors. These findings uncover a link between constitutive immune activity and tumorigenesis in intestinal stem cells.
Highlights
Endodermal tissue hosts an ancient and intimate relationship between multicellular organisms and the microbial world
We showed that constitutive immune signals alter the expression of Notch pathway regulators, disturb enteroendocrine cells (EEs) differentiation, and cause hyperplasia throughout the posterior midgut
Consistent with interactions between immune deficiency (IMD) and Notch, we found that constitutive IMD activity exacerbated the growth of Notch-deficient tumors
Summary
Endodermal tissue hosts an ancient and intimate relationship between multicellular organisms and the microbial world. Gut commensals provide factors that influence nutrition, development, and immunity in the host negotiate (Cho and Blaser, 2012). For their part, hosts invest energy and resources in the containment of gut microbes (Hooper et al, 2012). Germline-encoded innate immune systems are important for defense of the endoderm, a primary site of contact between multicellular organisms and their microbial environment. Characterization of innate immunity in endodermal tissues is essential for a full appreciation of the mechanistic basis for the restraint of gut microbes
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