This is a resubmission of an application previously reviewed in this study section. The principal investigator proposes to investigate the neuro-pathological and immunological aspects of tissues obtained from humans infested with the larval form of Taenia soleum. In addition she proposes to investigate an experimental cisticersosis (T crassiceps) in mice. The application has three Specific Aims. In the first Aim the principal investigator wishes to characterize the inflammatory response and the immunological reactions to T soleum larvae in the CNS of humans. She has arranged to obtain appropriately frozen larval excisions, cyst fluid and CSF samples of such patients from collaborators in Mexico (where the disease is far more prevalent). First she will determine the cell types present in the CNS material using immunohistochemistry specific for the cellular elements of the CNS. in addition Tg/d cells will be sought. Next she will define the adhesion molecules expressed on and in the region of the parasitic cysts. Chemokines and cytokine profiles will also be established. In addition to immunohistochemistry, she will use in situ hybridization and in situ PCR to localize these cytokines/chemokines in the inflammatory infiltrate. Special attention will be directed to cytokines believed responsible for immuno-suppression of the reaction. Finally, she will seek evidence of apoptosis or immune activation of the cells (native and infiltrating) in the vicinity of the larval cysts. The second Specific Aim is to attempt to correlate the findings of the first Specific Aim with the corresponding levels of cytokines in the CSF or peripheral blood.
Her final Aim i s to utilize a murine system of CNS larval infestation by T crassiceps and/or M corti to validate and render coherent her findings in the human tissues. This system will be much more controlled and manipulable. In addition, the scope of reagents available for these studies in a murine system should permit a more detailed dissection of the murine Teania system. Under this Aim she will first define the pathology, the inflammatory infiltrates, the cytokine production and adhesion molecule expression in infested mouse liver and brain tissue. (It is noted that T crassiceps does not infest brain, but M corti can be made to do so following intracerebral injection. In this system she can examine the effect on the immune response of the living parasite, and following administration of anti-helmenthic agents, observe the response to degenerating parasitic cysts. In a second part of this Aim, she will screen a variety of murine strains for variations in susceptibility to infestation by these organisms. Special attention will be directed toward mice deficient in IgE production which is believed important in defining the host-parasite relationship. Finally, she will utilize a variety of gene knock-out mice (IL4, IL10, TGFb, E-selectin, CD40 and IFNg knock outs will be available for study).

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
3R01NS035974-02S1
Application #
6053335
Study Section
Special Emphasis Panel (ZRG1 (01))
Program Officer
Kerza-Kwiatecki, a P
Project Start
1997-07-15
Project End
2000-06-30
Budget Start
1998-07-01
Budget End
1999-06-30
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Texas Health Science Center San Antonio
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
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; 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
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
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
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; 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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