Bacterial-modulated host immunity and stem cell activation for gut homeostasis

Abstract

Although it is widely accepted that dynamic cross-talk between gut epithelia and microorganisms must occur to achieve gut homeostasis, the critical mechanisms by which gut-microbe interactions are regulated remain uncertain. In this issue of Genes & Development, Buchon and colleagues (pp. 2333-2344) revealed that the reaction of the gut to microorganisms is not restricted to activating immune systems, but extends to integrated responses essential for gut tissue homeostasis, including self-renewal and the differentiation of stem cells. Further investigation of the connection between immune response and stem cell regulation at the molecular level in the microbe-laden mucosal epithelia will accelerate our understanding of the regulatory mechanisms of gut homeostasis and of the pathogenesis of diseases such as chronic inflammatory diseases and colorectal cancers.

Figure 1.

Hypothetical scheme for bacterial-modulated stem cell signaling. It is well-established that gut–microbe interactions induce different amounts of DUOX-dependent ROS production proportional to the microbial load and/or virulence (e.g., low chronic ROS production in the case of beneficial/routine interactions and high acute ROS production in the case of infectious/pathogenic interactions). Additionally, physical and chemical tissue damage may also directly induce ROS in a DUOX-dependent (as shown in zebrafish model) (Niethammer et al. 2009) and/or DUOX-independent manner. It remains to be elucidated whether microbe-induced ROS act as direct inducers of stem cell signaling or simply cause tissue damage that in turn signals to stem cells via other means. Given that tissue damage can also provoke ROS generation and that ROS can act both as cytotoxic molecules and signaling second messengers, one can speculate that both mechanisms are involved in stem cell signaling but are in operation in a context-dependent manner depending on spatial and temporal ROS concentration. See the text for more details about the putative redox-sensitive signaling modulation.