The long-term goal of this project is to characterize the immune response and associated pathology of neurocysticercosis (NCC). NCC is caused by the helminth parasite, Taenia solium, and is the most common parasitic disease of the central nervous system throughout the world. It is estimated that 50 million persons are infected, with an increasing number of patients in the U.S.A. During this study period, it is planned to study additional patients but in sufficient numbers to stratify them according to presentation and prognosis as well as age. Patient specimens (brain, cerebral spinal fluid (CSF), and serum) will be analyzed. The specimens, collectively, will be analyzed for cellular composition of CNS infiltrates, levels of cytokines (with emphasis on proinflammatory cytokines), chemokines, and other immune relevant molecules as the amount of specimen permits. Another major focus will involve further studies on the animal model for NCC. As gammadelta T cells are the major T cell subset in this infection, the P.I. will characterize their role using gammadelta T-cell deficient mice. Another aim is to focus on the pathology associated with the blood-brain barrier (BBB). Finally, the effects of the anti-helminthic drug albendazole on the immune response will be assessed with emphasis on granuloma formation. The experimental design for both the human and animal studies will include multiplex gene analysis, immunofluorescence, ELISA techniques, and immuno-electron microscopy. Wherever possible when using brain specimens, in situ analyses will be done because this allows for the assessment of the overall architecture including location of the organism, infiltrating cells, and surrounding brain tissue. These studies will provide basic information regarding immune responses in the CNS compared to the periphery, as well as clinical insights into disease mechanisms in NCC.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS035974-04
Application #
6199734
Study Section
Special Emphasis Panel (ZRG1-BDCN-4 (01))
Program Officer
Kerza-Kwiatecki, a P
Project Start
1997-07-15
Project End
2004-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
4
Fiscal Year
2000
Total Cost
$289,000
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Microbiology/Immun/Virology
Type
Other Domestic Higher Education
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Mishra, Pramod Kumar; Morris, Elizabeth G; Garcia, Jenny A et al. (2013) Increased accumulation of regulatory granulocytic myeloid cells in mannose receptor C type 1-deficient mice correlates with protection in a mouse model of neurocysticercosis. Infect Immun 81:1052-63
Mishra, Pramod Kumar; Teale, Judy M (2013) Changes in gene expression of pial vessels of the blood brain barrier during murine neurocysticercosis. PLoS Negl Trop Dis 7:e2099
Mishra, Pramod Kumar; Teale, Judy M (2012) Transcriptome analysis of the ependymal barrier during murine neurocysticercosis. J Neuroinflammation 9:141
Sharma, Jyotika; Mishra, Bibhuti B; Li, Qun et al. (2011) TLR4-dependent activation of inflammatory cytokine response in macrophages by Francisella elongation factor Tu. Cell Immunol 269:69-73
Mares, Chris A; Sharma, Jyotika; Li, Qun et al. (2011) Defect in efferocytosis leads to alternative activation of macrophages in Francisella infections. Immunol Cell Biol 89:167-72
Sharma, Jyotika; Mares, Chris A; Li, Qun et al. (2011) Features of sepsis caused by pulmonary infection with Francisella tularensis Type A strain. Microb Pathog 51:39-47
Mishra, Bibhuti B; Gundra, Uma Mahesh; Teale, Judy M (2011) STAT6ýýý/ýýý mice exhibit decreased cells with alternatively activated macrophage phenotypes and enhanced disease severity in murine neurocysticercosis. J Neuroimmunol 232:26-34
Gundra, Uma Mahesh; Mishra, Bibhuti B; Wong, Kondi et al. (2011) Increased disease severity of parasite-infected TLR2-/- mice is correlated with decreased central nervous system inflammation and reduced numbers of cells with alternatively activated macrophage phenotypes in a murine model of neurocysticercosis. Infect Immun 79:2586-96
Mares, Chris A; Sharma, Jyotika; Ojeda, Sandra S et al. (2010) Attenuated response of aged mice to respiratory Francisella novicida is characterized by reduced cell death and absence of subsequent hypercytokinemia. PLoS One 5:e14088
Mares, C A; Ojeda, S S; Li, Q et al. (2010) Aged mice display an altered pulmonary host response to Francisella tularensis live vaccine strain (LVS) infections. Exp Gerontol 45:91-6

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