Luminal neutrophils block pathogen attacks to help intestinal epithelium better fight Salmonella infections
Neutrophils enter the gut lumen during gut infections, but their exact function is still an enigma. A recent "PloS Pathogens" paper by the Hardt group (IMB) sheds light on this and reveals that Salmonella induced diarrhea, neutrophils form a physical barrier in front of the gut epithelium and reduce pathogen attack from the luminal side.
The intricate interplay between the microbiota and mucosal immune system is vital for safeguarding the intestine against enteric infections and maintaining homeostasis. Disruption of this harmonious defense mechanism elevates the susceptibility to inflammatory diseases. Pathogens like Salmonella enterica and Clostridioides difficile elicit distinct neutrophil responses, exemplified by crypt abscesses or pseudomembranous colitis, characterized by robust neutrophil accumulation and aggregate formation in the gut lumen. However, the precise role of these neutrophils, whether protective or detrimental, remains unclear.
To shed light on this enigma, we utilized mouse models of Salmonella Typhimurium infection. Our investigations unveiled that luminal neutrophils constitute a pivotal component of the orchestrated immune reaction to Salmonella invasion within the gut epithelium. In the absence of neutrophils, the relentless onslaught of pathogens upon epithelial cells overwhelms the system, resulting in heightened loss of these cells. Significantly, we underscore the criticality of intraluminal defense, particularly when the microbiota is disrupted or absent. In the context of germ-free mice devoid of neutrophil protection, the consequences are dire, culminating in the complete breakdown of the epithelial layer. This work provides new insights into the protective role of microbiota and intraluminal neutrophils, and how they together ensure the maintenance of epithelial barrier integrity against enteric infections.
Link to the paper in external page "PloS Pathogens".