RESUMEN
Intestinal peristalsis is a dynamic physiologic process influenced by dietary and microbial changes. It is tightly regulated by complex cellular interactions; however, our understanding of these controls is incomplete. A distinct population of macrophages is distributed in the intestinal muscularis externa. We demonstrate that, in the steady state, muscularis macrophages regulate peristaltic activity of the colon. They change the pattern of smooth muscle contractions by secreting bone morphogenetic protein 2 (BMP2), which activates BMP receptor (BMPR) expressed by enteric neurons. Enteric neurons, in turn, secrete colony stimulatory factor 1 (CSF1), a growth factor required for macrophage development. Finally, stimuli from microbial commensals regulate BMP2 expression by macrophages and CSF1 expression by enteric neurons. Our findings identify a plastic, microbiota-driven crosstalk between muscularis macrophages and enteric neurons that controls gastrointestinal motility. PAPERFLICK:
Asunto(s)
Motilidad Gastrointestinal , Tracto Gastrointestinal/citología , Tracto Gastrointestinal/microbiología , Macrófagos/metabolismo , Animales , Proteína Morfogenética Ósea 2/metabolismo , Receptores de Proteínas Morfogenéticas Óseas de Tipo II/metabolismo , Tracto Gastrointestinal/inervación , Tracto Gastrointestinal/fisiología , Técnicas In Vitro , Factor Estimulante de Colonias de Macrófagos , Ratones , Neuronas/metabolismo , Peristaltismo , Receptor de Factor Estimulante de Colonias de Macrófagos/metabolismo , Transducción de SeñalRESUMEN
Present in all organs, mononuclear phagocytes consist of a heterogeneous population of hematopoietic cells whose main role is to ensure tissue homeostasis through their ability to scavenge cell debris, promote tissue repair and maintain tolerance to self-antigens while simultaneously inducing innate and adaptive immune responses against foreign antigens that breach the tissue. The intestinal mucosa is particularly exposed to foreign antigen, through constant exposure to high loads of commensal bacteria and dietary antigens as well as providing a site of entry for viral and bacterial pathogens. The molecular mechanisms that control the intestinal ability to distinguish between "innocuous" and "dangerous" antigens remains poorly understood although it is clear that mononuclear phagocytes play a key role in this process. This review highlights recent advances in our understanding of heterogeneous origin of the mononuclear phagocytes that inhabit the intestinal mucosa and discusses how developmental diversity allows for functional diversity to ensure intestinal integrity.