Fig 1.
A paradigm of Th1/Th2 response during helminth infection.
During a Th2 cell-biased response, epithelial cell-derived cytokines such as TSLP and IL-33, in addition to tuft cell-derived IL-25, collectively result in the activation of type 2 response through Th2 cells and ILC2s. Once activated, these cells produce the type 2 cytokines IL-4, IL-5, and IL13 that in turn activate effector mechanisms for worm expulsion such as goblet cell hyperplasia, increased mucus production (Muc), muscle contractility, and production of RELM-β. In contrast, a Th1-biased response results in susceptibility. Activated IL-12-, IL-18-, and IL-27-induced Th1 cells (under some circumstances) robustly produce IFN-γ, which synergistically represses the type 2 response. IFN-γ, interferon gamma; ILC2, innate lymphoid cell 2; Muc, mucin; RELM-β, resistin-like molecules β; TSLP, thymic stromal lymphopoietin.
Fig 2.
The protective roles of a GC-Tfh response during helminth infection.
During early stages of helminth infection, DCs in the lamina propria process the parasite-derived antigen, which then migrate to the MLNs. In MLNs, the DCs alongside B cells interact with naive CD4 T cells that result in Th2 and Tfh cell differentiation. In the presence of specific signals, Th2 cells are then localised to the effector sites and are predominantly responsible for the effector type 2-mediated worm expulsion response. On the other hand, Tfh cells interact with activated B cells for the formation of GC reactions in the MLNs. In the DZ, the B cells undergo further proliferation and SHM, resulting in higher affinity of B cell receptors. The B cells then migrate to the LZ and are selected by Tfh cells via specific interactions and Tfh-derived cytokines such as IL-4 and IL-21, to return to the DZ. Such a process occurs in an iterative fashion in order to produce an effective antibody repertoire such as IgG1 and IgE. The GC-Tfh cells can also differentiate into effector Th2 cells and vice versa. The GC-derived B cells can develop into long-lived memory B cells (Image created with Biorender.com). DC, dendritic cell; DZ, dark zone; GC, germinal center; ILC2, innate lymphoid cell 2; LZ, light zone; MLN, mesenteric lymph node; SHM, somatic hypermutation.
Table 1.
Experiments using a passive immunization approach to study the role of antibodies during intestinal helminth infection.
Table 2.
Experiments using specific mouse models to study the role of antibodies and B cells during intestinal helminth infection.