Dr. Judy Teale
Neurocysticercosis (NCC), a parasitic disease of the central nervous system caused by the helminth Taenia solium. The long term goal of this project has been to characterize the host immune response and the pathology associated with NCC. Apart from analyses of brain specimens from NCC patients, we have developed a mouse model of NCC by intra-cranial infection with the related cestode, Mesocestoides corti. Our studies have shown that the parasite releases glycans with distinct sugar specificities that are taken up by host cells in the CNS environment in both human and murine NCC. Immunological events following recognition of these glycan antigens likely play a critical role in the immunopathogenesis of NCC. Parasite glycan induced regulatory responses involving myeloid derived suppressor cells (MDSCs) are thought to be key in host protection, however the receptors involved in this process are largely uncharacterized. C-type lectin receptors (CLRs) recognize glycan antigens of both pathogen and host origins and function in a wide variety of inflammatory and regulatory immune responses. Little is known regarding the expression of CLRs and their role in CNS infections which is the objective of this project. We hypothesize that parasite released glycans induce differential expression of CLRs which modulate the expression of effector molecules as well as activation and trafficking of leukocytes. We further hypothesize that CLRs differentially modulate functions of MDSCs that likely influence the immunopathology in murine NCC.
Alvarez, J.I., Krishnamurthy, J., Teale, J.M. 2009 Doxycycline Treatment Decreases morbidity and Mortality of Murine Neurocysticercosis: Evidence for Reduction of Apoptosis and Matrix Metalloproteinase Activity. Amer. J. of Path. 175(2): 685-95. PMID: 19574432.
Mishra B.B., Gundra U.M., Wong K., Teale J.M. 2009 MyD-88 deficient mice exhibit decreased parasite induced immune responses but reduced disease severity in a murine model of neurocysticersosis. Inf and Immun. PMID: 19786565.
Mishra B.B., Gundra U.M., Teale J.M. 2009 Toll-like receptors in CNS parasitic infections. Curr Top Microbiol Immunol. 336:83-104. PMID: 19688329
Alvarez, J.I., Mishra, B.B., Gundra, U.M., Mishra, P.K., Teale, J.M. 2010 Mesocestoides corti Intracranial infection as a murine model for Neurocysticercosis. Parasitology. PMID: 20109250
Mishra B.B., Gundra U.M., Teale J.M. 2010 Stat6 mice exhibit decreased dells with Alternatively activated macrophage phenotypes and enhanced disease severity in murine neurocytricercosis. J. of Neuroimmuno. Nov 2010. PMID: 21051093
Gundra U.M., Mishra B.B., Wong K., J.M. Teale. 2011 Increased disease severity of parasite infected TLR2-/- mice is correlated with a decreased and reduced number of cells with alternatively activated macrophage phenotypes in a murine model of neurocysticercosis. Inf and Immun . PMID: 21482681
Mishra, P.K., Teale, J.M. 2012 Transcriptome analysis of the ependymal barrier during murine neurocysticercosis. J. Neuroinflam. 9:141. PMID: 22731103