Haijun Tu

The intestinal muscularis is a multifunctional tissue that coordinates motility, immune responses, and tissue homeostasis through interactions among enteric neurons, smooth muscle cells (SMCs), and immune cells. Beyond its classical role in peristalsis, emerging evidence identifies the intestinal muscularis as an active regulatory hub integrating neural, immune, and microbial signals. Here, we review the anatomical organization, physiological functions, and pathological alterations in inflammatory bowel diseases, irritable bowel syndrome, infection, and Hirschsprung disease. We further highlight how disruption of integrated neuromuscular and immune networks drives pathological remodeling and discuss emerging concepts and future directions in muscularis biology.

Deleterious molecules or factors produced by pathogens can hinder the normal physiological functioning of organisms. In response to these survival challenges, organisms rely on innate immune signaling as their first line of defense, which regulates immune-responsive genes and antimicrobial peptides to protect against pathogenic infections. These genes are under the control of transcription factors, which are known to regulate the transcriptional activity of genes after binding to their regulatory sequences. Previous studies have employed Caenorhabditis elegans as a host–pathogen interaction model to demonstrate the essential role of different transcription factors in the innate immunity of worms. In this review, we summarize the advances made regarding the functioning of distinct transcription factors in the innate immune response upon pathogen infection. Finally, we discuss the open questions in the field, whose resolutions have the potential to expand our understanding of the mechanisms underlying the innate immunity of organisms.

Pathogen avoidance behaviour has been observed across animal taxa as a vital host-microbe interaction mechanism. The nematode Caenorhabditis elegans has evolved multiple diverse mechanisms for pathogen avoidance under natural selection pressure. We summarise the current knowledge of the stimuli that trigger pathogen avoidance, including alterations in aerotaxis, intestinal bloating, and metabolites. We then survey the neural circuits involved in pathogen avoidance, transgenerational epigenetic inheritance of pathogen avoidance, signalling crosstalk between pathogen avoidance and innate immunity, and C. elegans avoidance of non-Pseudomonas bacteria. In this review, we highlight the latest advances in understanding host-microbe interactions and the gut-brain axis.

Gap junctions mediate intercellular communications across cellular networks in the nervous and immune systems. Yet their roles in intestinal innate immunity are poorly understood. Here, we show that the gap junction/innexin subunit inx-14 acts in the C. elegans gonad to attenuate intestinal defenses to Pseudomonas aeruginosa PA14 infection through the PMK-1/p38 pathway. RNA-Seq analyses revealed that germline-specific inx-14 RNAi downregulated Notch/GLP-1 signaling, while lysosome and PMK-1/p38 pathways were upregulated. Consistently, disruption of inx-14 or glp-1 in the germline enhanced resistance to PA14 infection and upregulated lysosome and PMK-1/p38 activity. We show that lysosome signaling functions downstream of the INX-14/GLP-1 signaling axis and upstream of PMK-1/p38 pathway to facilitate intestinal defense. Our findings expand the understanding of the links between the reproductive system and intestinal defense, which may be evolutionarily conserved in higher organism.