Figure 4.

The intricate relationship between the GM and roundworms presents a dual-edged sword in the context of inflammation, necrosis, and apoptosis. While excretory/secretory (ES) products from roundworms encourage anti-inflammatory bacterial taxa and suppress pro-inflammatory ones, the complexity deepens with the Th2 immune response. This response, characterized by elevated levels of IL-4 and IL-13, stimulates goblet cells to increase mucus production, altering the gut lumen’s environment. Such changes support the proliferation of regulatory T-cells (Tregs) via TGF-β and IL-10 release, promoting an anti-inflammatory milieu strengthened by short-chain fatty acids like butyrate. However, this balance is precarious; any breakdown of the intestinal barrier can allow harmful microbial compounds such as lipopolysaccharides to infiltrate systemic circulation. The ensuing cascade involves reactive oxygen species and pro-inflammatory cytokines like TNF-α and IL-1β being released through TLR4 signaling in macrophages. Despite this turmoil, roundworms contribute to regulating immune cell apoptosis at a cellular level; they help sustain Treg survival through IL-10 and TGF-β signaling during infection. Ultimately, while specific mechanisms foster immunological tolerance and curb inflammation, they also highlight vulnerabilities that could exacerbate systemic inflammatory responses if not carefully modulated. This figure was generated using BioRender software version 04.