Gamma-delta T lymphocytes: Immunoregulatory and effector functions during murine neurocysticercosis (Taenia solium)

Neurocysticercosis is caused by the presence of Taenia solium metacestodes in the brain. The number of parasites, the location and degree of the host response define the severity of the disease. In order to analyze the immune response and immunopathology of the infection a mouse model was developed. In mouse brain the immune response revealed a large infiltration of γδ T cells, macrophages, and NK cells, αβ T cells, B cells, dendritic cells, mast cells to a lesser extent. A predominant Th1 pathway of cytokine response was detected. γδ T cells appeared to mediate the inflammatory response by producing IL2, 1L12, IL15 and IFN-γ. The immune response in the absence of γδ T cells revealed a decreased abundance of inflammatory cells and a mixed type1/type2 cytokine profile. A protective role of γδ T cells was evident by the fact that γδ−/− (TCRDKO) mice exhibited a disseminated infection. Furthermore γδ T cells were specifically accumulated in the brain of TCRDKO mice during adoptive transfer experiments. In contrast to the Thl inflammatory response influenced by γδ T cells, downregulation of IL12 and induction of IL4, IL10 and IL13 were detected in the process of parasite disintegration. During the process of granuloma formation a predominant Th2 profile of cytokine response was detected.; Chemokine and chemokine receptor expression analyses indicated that parasite infection induced a predominant abundance of CC chemokines (MCP-1, MIP-1α, MIPIP, RANTES and eotaxin). TCRDKO mice exhibited reduced abundance of these chemokines. Moreover CCR5 was greatly up regulated in wild type mice. Analysis of cellular response in CCR5−/− and MIP-1α−/− mice indicated that both were crucial for the CNS accumulation of γδ T cells.; Released Mesocestoides corti (MCS) and Taenia solium (TSF) antigens induced accumulation of γδ T cell in-vivo. Furthermore MCS, TSF induced activation of γδ T cells. Lipid extracts isolated from MCS and TSF induced γδ T cell activation in a CDId dependent manner.; γδ T cells play important immunoregulatory functions in the brain. This model represents a valuable approach to, study the immunopathology of NCC, and to determine the role of this immune subset in the human NCC.