Up to 20% of the global population develops gastrointestinal symptoms following a meal 1 , leading to decreased quality of life, significant morbidity and high medical costs. Although the interest of both the scientific and lay community has increased dramatically with the worldwide introduction of gluten-free and other diets, the underlying mechanisms leading to food-induced abdominal complaints remain largely unknown. Here we show that a bacterial infection and bacterial toxins can trigger an immune response leading to the production of dietary antigen-specific IgE antibodies in mice, a mechanism confined to the intestine. Subsequent oral ingestion of the respective dietary antigen results in increased visceral pain via an IgE-and mast cell-dependent mechanism. This aberrant pain signaling results from histamine receptor H1 (H1R)-mediated sensitization of visceral afferents. Moreover, in patients with irritable bowel syndrome (IBS), we show that injection of food antigens (gluten, wheat, soy and milk) into the rectosigmoid induces local edema and mast cell activation. Hence, we have unveiled and characterized a novel peripheral mechanism underlying food-induced abdominal pain, which creates new opportunities for the treatment of IBS and related abdominal pain disorders. MAIN TEXT:The mucosal immune system provides a balanced response to pathogens and harmless commensal bacteria or food antigens, thereby limiting unnecessary inflammation and concomitant tissue damage 2 . This is achieved by an active suppression of cellular and humoral responses to orally administered antigens, a mechanism referred to as oral tolerance 3 . Viral and bacterial infections can, however, interfere with tolerance to dietary antigens, thereby perturbing intestinal homeostasis 4 . An infectious gastroenteritis is a significant risk factor to develop IBS, defined as a constellation of abdominal pain and altered bowel patterns. Between 3 and 36% of enteric infections lead to new onset IBS 5 , while up to 17% of IBS patients report that their symptoms started Supplementary information included as a separate pdf file and videos (Supplementary Information Video 1-4). EXTENDED DATA LEGENDS: Extended Data Fig. 1. Extended analysis of the OVA-specific immune response and VHS in postinfectious mice. a, b, diarrhea development quantification by (a) water content in feces and (b) whole-gut transit time upon gavage of carmine red dye in OVA/sham + OVA, OVA/infected + OVA (n = 10/group) mice. c, quantification of OVA-specific IgE in intestinal homogenates of OVA/sham + OVA, saline/infected + OVA,
Aggression is a universal social behavior important for the acquisition of food, mates, territory, and social status. Aggression in Drosophila is context-dependent and can thus be expected to involve inputs from multiple sensory modalities. Here, we use mechanical disruption and genetic approaches in Drosophila melanogaster to identify hearing as an important sensory modality in the context of intermale aggressive behavior. We demonstrate that neuronal silencing and targeted knockdown of hearing genes in the fly's auditory organ elicit abnormal aggression. Further, we show that exposure to courtship or aggression song has opposite effects on aggression. Our data define the importance of hearing in the control of Drosophila intermale aggression and open perspectives to decipher how hearing and other sensory modalities are integrated at the neural circuit level.A ggression is one of the most important social behaviors in nature, ensuring reproduction and survival when competing for food, territory, or mating partners (1). Aggression is a complex behavior shaped by many factors, including a complex genetic architecture, the integration of various neurotransmitter and hormone systems, and a range of environmental factors (2).Correct integration and processing of sensory information are crucial to evoke an appropriate behavioral response. Previous studies have implicated different sensory modalities in the regulation of aggressive behavior in Drosophila melanogaster, including the olfactory, gustatory, and visual systems (3-6).Another important sensory modality in Drosophila is hearing. Stereotypic sound patterns generated by wing vibration and their behavioral significance have been extensively studied in the context of Drosophila courtship (7-12). On the contrary, nothing is known about the impact of hearing on aggressive behavior. Furthermore, although agonistic sound pulses are known to be generated during aggressive encounters, it is unknown whether they serve as acoustic communication signals to modulate behavior (13).The Drosophila auditory organ, Johnston's organ (JO), is situated in the fly's antenna (Fig. 1A) (14-17). Antennal displacement leads to activation of ∼500 chordotonal stretch-receptor neurons in the JO, which contains AB neurons responsive to sound-evoked vibrations and CE neurons sensitive to sustained antennal deflections caused by gravity and wind (Fig. 1A) (18). The sensory neuron subclasses each innervates a particular region of the antennal mechanosensory and motor center (AMMC), the primary processing center for auditory input in the fly brain (18).In this study, we use mechanical disruption and genetic approaches in D. melanogaster to identify hearing as an important sensory modality in the context of intermale aggressive behavior. We show that neuronal silencing and targeted knockdown of hearing genes in the fly's auditory organ induce abnormal aggression. Further, we show that exposure to courtship or aggression song has opposite effects on aggression. Our data provide evidence on the r...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.