This project's long-term aim is to gain understanding of immune responses in cysticercosis, with a view to develop novel immunotherapies. Cysticercosis, due to invasion of the pork tapeworm larvae Taenia solium, is an emerging disease in wealthier nations and a major cause of morbidity in endemic areas including South America and India. Epilepsy is the most prominent clinical manifestation and is due to parasitic cysticerci in the central nervous system (CNS). In the USA, cysticercosis is increasingly common in part because of the influx of immigrants. The initial pathological response in cysticercosis is the formation of eosinophil-rich inflammatory granulomas. Drug treatment may eliminates cysts but is associated with transient leukocyte influx into the CNS leading to clinical deterioration and sometimes death. In order to develop novel therapeutic strategies and to limit cellular influx, information is required about immune responses to this infection. There have been very few previous studies. On the basis of preliminary observations, the aim of this project is to collect in vivo data from patients (plus controls) on the presence of proinflammatory and chemotactic cytokines in infected patients. Such cytokines are critical in initiating successful immunity and in controlling cellular influx to sites of infection. We shall measure by ELISA, cytokine concentrations in plasma and cerebrospinal fluid. The ability of patient leukocytes to express genes for (northern analysis) and secrete such cytokines will be determined. Patterns of cytokine secretion during treatment will be examined to determine if anti- cytokine therapies are a real possibility. Finally, pilot work will develop an in vitro model of infection examining interactions between cysticerci and macrophages. The information will provide essential data needed to understand immunity to cysticercosis and for development of new treatments.
| Uddin, Jasim; Gonzalez, Armando E; Gilman, Robert H et al. (2010) Mechanisms regulating monocyte CXCL8 secretion in neurocysticercosis and the effect of antiparasitic therapy. J Immunol 185:4478-84 |
| Uddin, Jasim; Gonzalez, Armando E; Gilman, Robert H et al. (2006) Neurocysticercal antigens stimulate chemokine secretion from human monocytes via an NF-kappaB-dependent pathway. Microbes Infect 8:1732-40 |
| Uddin, Jasim; Garcia, Hector H; Gilman, Robert H et al. (2005) Monocyte-astrocyte networks and the regulation of chemokine secretion in neurocysticercosis. J Immunol 175:3273-81 |
| Garcia, H H; Gonzalez, A E; Gilman, R H et al. (2002) Circulating parasite antigen in patients with hydrocephalus secondary to neurocysticercosis. Am J Trop Med Hyg 66:427-30 |
| Garcia, H H; Parkhouse, R M; Gilman, R H et al. (2000) Serum antigen detection in the diagnosis, treatment, and follow-up of neurocysticercosis patients. Trans R Soc Trop Med Hyg 94:673-6 |
