The induction of T helper type 1 response by cytokine gene transfection protects mice against secondary hydatidosis

Abstract

Infection of BALB/c mice with protoscoleces of Echinococcus granulosus constitutes a model for the study of secondary hydatidosis (SH) and the associated immune response in immunization and infection trials. This study aimed at testing the efficacy of the cytokine gene expression approach to modulate the immune response and the magnitude of cyst development in mice with secondary hydatidosis. At the time of cyst development (28 days post infection), mice were injected intramuscularly with an expression vector containing murine promoter and carrying the open reading frames of IFN-gamma, IL-12 (Th1 cytokines), or IL-4 (Th2 cytokine). Assessment of cyst load at 22 weeks of infection showed a significant reduction in cyst load in mice injected with IFN-gamma and IL-12 genes at 60% and 47%, respectively. In contrast, the IL-4-gene-injected mice displayed six times higher cyst load in comparison to control-infected mice (injected with empty plasmids). Parasite-specific IgG2a peaked in IL-12-gene-injected mice at week 7 of infection (3 weeks after gene transfection), whereas in IFN-gamma-gene-injected mice IgG2a started to elevate after week 9 and continued to increase steadily until the termination of the experiment (22 weeks post infection). In contrast, in IL-4-gene-transfected mice, the IgG1 elevation started after week 9 and continued steadily thereafter. In conclusion, a significant high protection rate against secondary hydatidosis in BALB/c mice was accompanied with the induction of Th1 response. Moreover, in vivo IL-12 gene expression induced earlier IgG2a in comparison to IFN-gamma.

Immunology and Immunodiagnosis of Cystic Echinococcosis: An Update

“…Studies with mouse models to overexpress cytokines by inducing cytokine expression vectors showed that IL-12 and IFN-gamma induce a parasite-specific IgG2a response in mice infected with protoscoleces of E. granulosus whereas in IL-4-gene-transfected mice, IgG1 was elevated, indicating that IgG1 and IgG2 antibody isotypes are regulated by Th1 and Th2 cytokines, respectively [43]. …”

“…Mice injected with a vector expressing IL-4 displayed six times higher cyst load than the load in control mice [43], indicating IL-4 plays an important role in hydatid cyst development in the mammalian host.…”

Mechanisms of Immunity in Hydatid Disease: Implications for Vaccine Development

“…Mice injected with an expression vector encoding IL-12 (20) or treated with rIL-12 (21) were protected against secondary CE and AE, respectively, and this was accompanied by a Th1 response. TLR is believed to play a key role in the innate immune system, but there is limited information on its involvement in innate resistance against Echinococcus infection.…”

IL-4 gene expression in adventitial layer (fibrous layer) of hepatic ovine and bovine hydatid cysts

“…Mice injected with a vector expressing IL-4 showed higher cyst load than the load in control mice (Al-Qaoud and Abdel-Hafez 2008). So IL-4 may play an important role in hydatid cyst development in the mammalian host (Zhang et al 2011).…”