RESUMO
Amino acid availability is monitored by animals to adapt to their nutritional environment. Beyond gustatory receptors and systemic amino acid sensors, enteroendocrine cells (EECs) are believed to directly percept dietary amino acids and secrete regulatory peptides. However, the cellular machinery underlying amino acid-sensing by EECs and how EEC-derived hormones modulate feeding behavior remain elusive. Here, by developing tools to specifically manipulate EECs, we find that Drosophila neuropeptide F (NPF) from mated female EECs inhibits feeding, similar to human PYY. Mechanistically, dietary L-Glutamate acts through the metabotropic glutamate receptor mGluR to decelerate calcium oscillations in EECs, thereby causing reduced NPF secretion via dense-core vesicles. Furthermore, two dopaminergic enteric neurons expressing NPFR perceive EEC-derived NPF and relay an anorexigenic signal to the brain. Thus, our findings provide mechanistic insights into how EECs assess food quality and identify a conserved mode of action that explains how gut NPF/PYY modulates food intake.
Assuntos
Ingestão de Alimentos , Células Enteroendócrinas , Ácido Glutâmico , Neuropeptídeos , Peptídeo YY , Animais , Células Enteroendócrinas/metabolismo , Feminino , Neuropeptídeos/metabolismo , Neuropeptídeos/genética , Ingestão de Alimentos/fisiologia , Peptídeo YY/metabolismo , Ácido Glutâmico/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Drosophila melanogaster/metabolismo , Comportamento Alimentar/fisiologia , Receptores de Glutamato Metabotrópico/metabolismo , Neurônios Dopaminérgicos/metabolismo , DietaRESUMO
The gut must perform a dual role of protecting the host against toxins and pathogens while harboring mutualistic microbiota. Previous studies suggested that the NADPH oxidase Duox contributes to intestinal homeostasis in Drosophila by producing reactive oxygen species (ROS) in the gut that stimulate epithelial renewal. We find instead that the ROS generated by Duox in the Malpighian tubules leads to the production of Upd3, which enters the gut and stimulates stem cell proliferation. We describe in Drosophila the existence of a countercurrent flow system, which pushes tubule-derived Upd3 to the anterior part of the gut and stimulates epithelial renewal at a distance. Thus, our paper clarifies the role of Duox in gut homeostasis and describes the existence of retrograde fluid flow in the gut, collectively revealing a fascinating example of inter-organ communication.
Assuntos
Proteínas de Drosophila , Drosophila melanogaster , Mucosa Intestinal , Túbulos de Malpighi , Espécies Reativas de Oxigênio , Animais , Túbulos de Malpighi/metabolismo , Proteínas de Drosophila/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Mucosa Intestinal/metabolismo , Drosophila melanogaster/metabolismo , NADPH Oxidases/metabolismo , Oxidases Duais/metabolismo , Oxidases Duais/genética , Proliferação de Células , Homeostase , Drosophila/metabolismoRESUMO
While largely neglected over decades during which adaptive immunity captured most of the attention, innate immune mechanisms have now become central to our understanding of immunology. Innate immunity provides the first barrier to infection in vertebrates, and it is the sole mechanism of host defense in invertebrates and plants. Innate immunity also plays a critical role in maintaining homeostasis, shaping the microbiota, and in disease contexts such as cancer, neurodegeneration, metabolic syndromes, and aging. The emergence of the field of innate immunity has led to an expanded view of the immune system, which is no longer restricted to vertebrates and instead concerns all metazoans, plants, and even prokaryotes. The study of innate immunity has given rise to new concepts and language. Here, we review the history and definition of the core concepts of innate immunity, discussing their value and fruitfulness in the long run.
Assuntos
Imunidade Inata , Memória Imunológica , Animais , Invertebrados , Imunidade Adaptativa , VertebradosRESUMO
7An efficient immune system must provide protection against a broad range of pathogens without causing excessive collateral tissue damage. While immune effectors have been well characterized, we know less about the resilience mechanisms protecting the host from its own immune response. Antimicrobial peptides (AMPs) are small, cationic peptides that contribute to innate defenses by targeting negatively charged membranes of microbes. While protective against pathogens, AMPs can be cytotoxic to host cells. Here, we reveal that a family of stress-induced proteins, the Turandots, protect the Drosophila respiratory system from AMPs, increasing resilience to stress. Flies lacking Turandot genes are susceptible to environmental stresses due to AMP-induced tracheal apoptosis. Turandot proteins bind to host cell membranes and mask negatively charged phospholipids, protecting them from cationic pore-forming AMPs. Collectively, these data demonstrate that Turandot stress proteins mitigate AMP cytotoxicity to host tissues and therefore improve their efficacy.