MECHANISMS OF CHLAMYDIAL EVASION OF IMMUNE RECOGNATION

Project: Research project

Project Details

Description

Human chlamydial infections are recognized as the leading cause of many important sexually transmitted diseases worldwide. The development of chlamydial diseases is largely due to persistent intracellular infection by the organisms. Chlamydial evasion of host immune response may contribute to the persistence of chlamydial infection. We found that chlamydia has evolved the ability to evade immune recognition by inhibiting both MHC class I and class II antigen expression, which is correlated with degradation of transcription factors required for MHC gene activation. We further found that a chlamydia-specific proteasome-like activity in chlamydia-infected cell cytosolic fraction is responsible for the transcription factor degradation. We hypothesize that chlamydia may secrete a factor(s) with the unique proteasome-like activity into host cell cytosol for evading immune recognition mechanisms. We designated this factor as chlamydial proteasome-like activity factor (CPAF). To test our hypothesis, we propose (1) to purify and to identify CPAF, (2) to understand how CPAF works including determining its subcellular location, intracellular trafficking, binding specificity, potential cofactors and function domains and (3) to search for inhibitors for blocking the enzymatic activity of CPAF using a phage-displayed peptide library plus affinity selection approach. These studies will provide essential information for understanding the molecular mechanisms of chlamydial pathogenesis and developing effective strategies for preventing chlamydial persistence and controlling chlamydia-induced diseases.
StatusFinished
Effective start/end date7/15/0011/30/16

Funding

  • National Institutes of Health: $371,557.00
  • National Institutes of Health: $349,263.00
  • National Institutes of Health: $369,715.00
  • National Institutes of Health: $339,510.00
  • National Institutes of Health: $346,086.00
  • National Institutes of Health: $371,557.00
  • National Institutes of Health: $356,423.00
  • National Institutes of Health: $289,000.00
  • National Institutes of Health: $339,000.00
  • National Institutes of Health: $289,000.00
  • National Institutes of Health: $339,510.00
  • National Institutes of Health: $371,557.00
  • National Institutes of Health: $310,250.00
  • National Institutes of Health: $289,000.00
  • National Institutes of Health: $339,000.00

ASJC

  • Medicine(all)
  • Immunology and Microbiology(all)

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