concanavalin-a and Cysticercosis

Parasite-induced immunosuppression is believed to play a significant role in the pathology of cysticercosis, a disease caused by the larval stage of cestode parasites. The biochemical basis for immunoregulation by Taenia crassiceps in experimental cysicercosis is unknown. In order to determine whether or not excretory/secretory (E/S) products from the parasite have the ability to regulate host immune function, the activity of these products was examined. Excretory/secretory products from larvae early in the infection were found to suppress T cell proliferative responses in vitro as well as the production of IFN-gamma and IL-4. In contrast, E/S products secreted from larvae harvested late in infection were not suppressive. Electrophoretic analysis of E/S products revealed both qualitative and quantitative differences in the pattern of proteins produced by larvae taken from an early infection versus those taken from a chronic infection. The viability of parasites taken from an early infection was greatly reduced compared to those taken from chronically infected mice, suggesting a change in the nature of the host immune response to the parasite during the course of the infection. The proliferative activity and cytokine profiles of host immune cells were examined. Both mesenteric lymph node cells and peritoneal exudate cells were found to produce high levels of both IFN-gamma and IL-4, consistent with the high levels of these cytokines in sera of chronically infected animals. Chronic infection with Taenia crassiceps therefore is characterized by high levels of production of both Th1 and Th2 cytokines by host cells.

Topics: Age Factors; Animals; Ascitic Fluid; Cell Division; Concanavalin A; Cysticercosis; Down-Regulation; Electrophoresis, Polyacrylamide Gel; Female; Helminth Proteins; Interferon-gamma; Interleukin-4; Larva; Lymph Nodes; Mesentery; Mice; Mice, Inbred BALB C; T-Lymphocytes; Taenia; Time Factors

Helminth infections are frequently massive, chronic and strong inductors of Th2-type cytokines. This implies that infection by such parasites could alter the susceptibility to subsequent infections by other pathogens, particularly intracellular parasites. We therefore explored whether a persistent infection, caused by Taenia crassiceps cysticerci, in BALB/c mice could affect susceptibility to a later infection by Trypanosoma cruzi. We found that the presence of the cysticerci indeed modified the immune response and the susceptibility to T. cruzi, and that these modifications depended on the time-course evolution of the initial infection. Coinfection with the protozoan in the early stages of the helminth infection, induced a delay on the onset of parasitaemia, early specific production of IFN-gamma and high specific production of IL-4. A significant increase in susceptibility to T. cruzi was observed only when mice were coinfected in late stages when the helminth load is greater and a Th2 type response against it is predominant. The in vitro specific response to T. cruzi antigens was then characterized by low levels of both IFN-gamma and IL-4. These findings suggest that chronic helminth infections could potentially have a significant influence over the immune response and hence susceptibility to other pathogens.

Topics: Animals; Antibody Specificity; Antigens, Helminth; Chagas Disease; Concanavalin A; Cysticercosis; Cytokines; Female; Lymphocyte Activation; Lymphocytes; Mice; Mice, Inbred BALB C; Parasitemia; Spleen

Several biological factors are involved in susceptibility and resistance to murine cysticercosis. A substantial body of evidence implies prostaglandins as potent regulators of immune responses during parasitic diseases. Here we evaluated the role played by prostaglandin E2 in cysticercosis. Mice were treated in vivo with prostaglandin E2 or with indomethacin (a prostaglandin E2 synthesis inhibitor) before infection. Parasite growth was enhanced by prostaglandin treatment, which provoked poor Con-A responses, low Th1-type cytokines secretion, and high levels of IL-6 and IL-10. In contrast, mice receiving indomethacin showed a reduction in parasite load parallel to a strong Con-A response and high levels of IL-2 and IFN-gamma, concomitantly with a decrease in IL-4, IL-6 and IL-10 production. Indirect in vitro studies suggest that an important source of prostaglandin E2 production could be related to host's adherent cells. However, prostaglandin E2 from parasite origin cannot be discarded.

Topics: Animals; Concanavalin A; Cyclooxygenase Inhibitors; Cysticercosis; Cytokines; Dinoprostone; Disease Susceptibility; Female; Indomethacin; Lymphocyte Activation; Mice; Mice, Inbred BALB C; Spleen; Taenia; Th2 Cells