Regulatory T Cells as an Escape Mechanism to the Immune Response in Taenia crassiceps Infection

Abstract

Murine cysticercosis by Taenia crassiceps is a model for human neurocysticercosis. Genetic and/or immune differences may underlie the higher susceptibility to infection in BALB/cAnN with respect to C57BL/6 mice. T regulatory cells (Tregs) could mediate the escape of T. crassiceps from the host immunity. This study is aimed to investigate the role of Tregs in T. crassiceps establishment in susceptible and non-susceptible mouse strains. Treg and effector cells were quantified in lymphoid organs before infection and 5, 30, 90, and 130 days post-infection. The proliferative response post-infection was characterized in vitro. The expression of regulatory and inflammatory molecules was assessed on days 5 and 30 post-infection. Depletion assays were performed to assess Treg functionality. Significantly higher Treg percentages were observed in BALB/cAnN mice, while increased percentages of activated CD127+ cells were found in C57BL/6 mice. The proliferative response was suppressed in susceptible mice, and Treg proliferation occurred only in susceptible mice. Treg-mediated suppression mechanisms may include IL-10 and TGFβ secretion, granzyme- and perforin-mediated cytolysis, metabolic disruption, and cell-to-cell contact. Tregs are functional in BALB/cAnN mice. Therefore Tregs could be allowing parasite establishment and survival in susceptible mice but could play a homeostatic role in non-susceptible strains.

Proteomic analysis of Taenia solium cysticercus and adult stages

“…This is associated with the exposure and intensity of infection as well as the developmental stage of the parasite and induced immune response. It may also be related to the inhibitory effect of T regulatory cells ( 8 – 10 ). Until now, however, it is unknown which parasitic molecules are responsible for these effects.…”

Taenia crassiceps Cysticercosis in a Wild Muskrat and a Domestic Dog in the Northeastern United States

“…Taenia crassiceps cysticercosis has been shown to drive sex hormone changes in mice and result in higher levels of sex steroids in both female and male mice [ 23 ]. As a model for human neurocysticercosis, T. crassiceps has been utilized to investigate the functions of T regulatory cells in facilitating parasitic establishment and lymphoproliferation in immunocompetent hosts [ 24 ]. Previous studies have revealed that MHC Qa-2 antigen in transgenic mice confers resistance to T. crassiceps cysticercosis [ 25 ].…”

Differential Protein Expression of Taenia crassiceps ORF Strain in the Murine Cysticercosis Model Using Resistant (C57BL/6) Mice

“…Taenia solium and T. crassiceps cysticerci cause cysticercosis in humans, pigs, and mice. Their establishment and survival depend on the environment encountered in hosts [ 5 , 6 , 7 ]. It has been demonstrated that BALB/c mice are more susceptible to parasite infection than C57BL/6 mice [ 5 ].…”

“…Because of the close phylogenetic relationship between Taenia crassiceps and T. solium and their antigenic and genomic similarity, the murine cysticercosis model for T. crassiceps has been widely used to study several physiological aspects of cysticercosis [ 2 , 3 , 4 ]. The resistance and susceptibility to T. crassiceps infections have been associated with the endocrine, genetic, and immune response in mice [ 5 , 6 , 7 ]. The susceptible BALB/c mouse favors a Th2 response and parasites’ growth with high levels of interleukin 4 (IL-4), IL-10 IL-13, IL-9, and transforming growth factor-beta (TGF-β), whereas the resistant C57BL/6 mouse develops a predominant Th1 response that limits the parasitic growth [ 8 , 9 , 10 , 11 ].…”

“…On the other hand, the immune response is influenced by parasite molecules. Cysticerci secretion/excretion (E/S) products promote a Th2 response with alternatively activated macrophages and T regulatory (Treg) cells in BALB/c mice [ 7 , 12 , 13 , 14 ]. Likewise, other parasite molecules drive toward the Th1 response with high levels of gamma interferon (IFN-γ) and IL-2, such as the cysticerci peptides KETc-1, KETc-2, and the enzyme glutathione transferases (SGSTF) [ 15 , 16 ].…”