Fasciola hepatica infection downregulates Th1 responses in mice

Abstract

Immune responses induced with helminth parasites have been extensively studied, but there is limited information on those to Fasciola hepatica, especially on the subtype of T cell induced with this parasite. We investigated the local and systemic T cell responses of different strains of mice following oral infection with doses of metacercariae from F. hepatica. Spleen cells from BALB/c and 129Sv/Ev mice given a low-dose (5 metacercariae) infection exhibited a Th2 response, producing high levels of the cytokines IL-4 and IL-5, and low levels of IFN-gamma and IL-2. In contrast, C57BL/6 mice showed a mixed Th1/Th2 response. A more marked polarization to a Th2 response was observed in BALB/c, 129Sv/Ev exposed to a high-dose (15 metacercariae) infection and the C57BL/6 mice also exhibited a clear Th2 response. IL-4 defective (IL-4-/-) C57BL/6 mice infected with 5 metacercariae produced less IFN-gamma and more IL-5 compared to their wild-type C57BL/6 counterparts, suggesting that IL-4 is important in establishing the Th2 type response in murine fasciolosis. However, the secretion of IFN-gamma and IL-2 was completely suppressed in the high-dose infection and this was also observed in IL-4-/- mice. Thus, liver flukes may secrete molecules that downregulate Th1 responses. T cell responses in the mesenteric (MLN) and hepatic lymph nodes (HLN) were also examined since newly excysted juveniles infect through the intestinal wall of their host before migrating to the hepatic tissue. Cells from both MLN and HLN secreted higher levels of IL-4 and IL-5 compared to spleen cells. We also observed a difference in cytokine profiles secreted by the MLN and HLN, which may reflect responses to antigens liberated by newly excysted juveniles and hepatic stage parasites, respectively.

Fasciola hepatica tegumental antigens induce anergic‐like T cells via dendritic cells in a mannose receptor‐dependent manner

“…Splenocytes isolated in mice from all groups produce significant levels of cytokines when treated with PMA/anti-CD3 (Fig. 1A-D) and no significant differences were observed between groups except IFN-γ where significant difference were observed between control and infected groups (data not shown; p < 0.001), which supports previously published findings [17].…”

“…Splenocytes isolated in mice from all groups produce significant levels of cytokines when treated with PMA/anti-CD3 (Fig. 1A-D) and no significant differences were observed between groups except IFN-γ where significant difference were observed between control and infected groups (data not shown; p < 0.001), which supports previously published findings [17].The lack of IL-2 in CD4 + T cells from F. hepatica-infected mice alters proliferation but not apoptosis IL-2 is essential for the differentiation of effector T cells into Thsubsets [22] and is involved in numerous other important roles such as T-cell proliferation or programmed cell death [23]. Splenocytes isolated from F. hepatica-infected mice failed to produce significant levels of IL-2 after restimulation with FhTeg and therefore it is possible that this lack of IL-2 could inhibit CD4 + T-cell proliferation or induce programme cell death.…”

“…Similar to other helminths, infection generally leads to potent Th2/Tregulatory response with high levels of IL-5, IL-4, and IL-10 observed, while protective Th1 cytokines like IFN-γ are suppressed within hours post infection. Fasciola hepatica infection in mouse models resembles immune responses observed in the natural host with a decrease in protective Th1 immune responses and an increase in Th2/Treg-driven responses with enhanced numbers of M2-like macrophages, mast cells, and eosinophils [17][18][19].…”

Early hepatic immune response in rats infected with Fasciola hepatica

“…If, as suggested by the murine S. mansoni and Trichinella spiralis models, Th1 cell-based effector mechanisms limit fluke survival, the suppression of these responses may be of crucial biological importance to helminth parasites. The suppression of the Th1 response by F. hepatica has been reported in several previous studies [3,23]. Induction of the "wrong" set of cytokines may inhibit other responses that are potentially more damaging for the parasite [19].…”

Fasciola hepatica Tegumental Coat Impairs Mast Cells’ Ability To Drive Th1 Immune Responses

“…We have shown previously that IL-4 2/2 mice, which are predisposed toward a Th1 immune response, are less susceptible to F. hepatica infection, with reduced liver damage, compared with IFN-gR 2/2 mice, which elicited strong Th2 responses and are highly susceptible to infection (39). Vaccine efficacy using F. hepatica excretorysecretory molecules or using recombinant F. hepatica secretory enzymes is associated with enhanced lymphocyte proliferation and IFN-g expression (10,40).…”