Figure 1
Intestinal helminths initially trigger a type 2 immune response through multiple mechanisms. Helminths damage tissue during feeding and migration in the intestine, which in turn can trigger the release of danger-associated molecular patterns (DAMPs) and cytokine alarmins (interleukin (IL)-25, thymic stromal lymphopoietin (TSLP), and IL-33). These alarmins then activate innate lymphoid cells and likely other cell populations that support the development of a type 2 innate immune response, which in turn provides necessary signals for the development of type 2 adaptive immunity. Excretory/secretory (ES) products released by helminths also promote the type 2 immune response through stimulation of cytokine alarmins and through effects on dendritic cells (DCs) that inhibit their capacity to support T helper type 1 (Th1) cell differentiation while promoting Th2 cell and T regulatory cell development in the draining lymph nodes. At the site of infection, the type 2 immune microenvironment likely sustains activation of Th2 effector cell and T regulatory cells. Together tissue damage and ES products, in the absence of strong Toll-like receptor (TLR) signaling, are likely primary stimuli that together trigger and help maintain a robust multicomponent type 2 response. Effects of helminths on the microbiome may also influence mucosal and systemic inflammatory responses. TGF-β, transforming growth factor beta.
