The focus of this proposal is to understand the immune response to pyogenic bacteria, such as S. aureus, in the pathogenesis of experimental brain abscess. This study may lead to identification of host and bacterial factors that play a key role in brain abscess development and pathology. First, they will evaluate, using S. aureus (one of the main etiological agents of brain abscess in humans,) the host immune responses in the central nervous system (CNS) parenchyma. They will use a rodent experimental model, and examine cytokines and chemokines elicited in response to bacterial challenge, the cellular origin(s) of these mediators within the CNS, and the response of primary astrocytes and microglia. Next, they will evaluate the relation of bacterial virulence factors in abscess pathogenesis. They will evaluate the role of virulence factors expressed in the CNS and what effect they have on the host immune response to infection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
7R01NS040730-02
Application #
6481127
Study Section
Special Emphasis Panel (ZRG1-BDCN-3 (01))
Program Officer
Kerza-Kwiatecki, a P
Project Start
2001-01-05
Project End
2003-11-30
Budget Start
2001-07-01
Budget End
2001-11-30
Support Year
2
Fiscal Year
2001
Total Cost
$119,830
Indirect Cost
Name
University of Arkansas for Medical Sciences
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
City
Little Rock
State
AR
Country
United States
Zip Code
72205
Hanamsagar, Richa; Aldrich, Amy; Kielian, Tammy (2014) Critical role for the AIM2 inflammasome during acute CNS bacterial infection. J Neurochem 129:704-11
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Xiong, Juan; Burkovetskaya, Maria; Karpuk, Nikolay et al. (2012) IL-1RI (interleukin-1 receptor type I) signalling is essential for host defence and hemichannel activity during acute central nervous system bacterial infection. ASN Neuro 4:
Hanamsagar, Richa; Hanke, Mark L; Kielian, Tammy (2012) Toll-like receptor (TLR) and inflammasome actions in the central nervous system. Trends Immunol 33:333-42
Liu, Yutong; Sajja, Balasrinivasa R; Uberti, Mariano G et al. (2012) Landmark optimization using local curvature for point-based nonlinear rodent brain image registration. Int J Biomed Imaging 2012:635207
Vidlak, Debbie; Kielian, Tammy (2012) Differential effects of interleukin-17 receptor signaling on innate and adaptive immunity during central nervous system bacterial infection. J Neuroinflammation 9:128
Holley, Monica M; Kielian, Tammy (2012) Th1 and Th17 cells regulate innate immune responses and bacterial clearance during central nervous system infection. J Immunol 188:1360-70
Hanke, Mark L; Kielian, Tammy (2011) Toll-like receptors in health and disease in the brain: mechanisms and therapeutic potential. Clin Sci (Lond) 121:367-87

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