October 9 - 12, 2012
Building 10 & Natcher Conference Center
- General Schedule of Events
- Opening Plenary Session
- Concurrent Symposia Sessions
- Poster Sessions
- National Graduate Student Research Conference
- FARE Award Ceremony
- Special Exhibits on Resources for Intramural Research
- TSA Research Festival Exhibit Show
- Clinical Center Tours
- Research Festival Committees
- Past Research Festivals
IRF8 is a central coordinator of autophagy required for clearance of infectious bacteria in macrophages
| Friday, November 08, 2013 — Poster Session IV | |||
|---|---|---|---|
2:00 p.m. – 4:00 p.m. |
FAES Academic Center (Upper-Level Terrace) |
NICHD |
IMMUNO-8 |
* FARE Award Winner
Authors
- M Gupta
- D.M Shin
- L Ramakrishna
- H.C Morse
- D.J Goussetis
- L.C Platanias
- H Xiong
- K Ozato
Abstract
Autophagy plays a pivotal role in innate and adaptive immunity. It is involved in the clearance of intracellular pathogens in macrophages. Factors involved in the regulation of autophagy in macrophages cells are not understood. In this study we found that Interferon Regulatory Factor 8 (IRF8), a transcription factor essential for myeloid cell function, plays a critical role in full execution of Interferon-γ (IFN-γ)/Toll like receptor (TLR) signal induced autophagy in macrophages. Our analysis revealed that in response to IFN-γ & TLR stimulation, the expression of crucial autophagy-related genes are induced in WT macrophages but not in IRF8-/- macrophages. The expression of the above genes in Irf8-/- macrophages can be rescued by Irf8 gene transfer. Autophagosomes, unique structure formed during autophagy, increases in the WT macrophages upon stimulation but not in Irf8-/- macrophages. Furthermore, degradation of intracellular ubiquitinated proteins is defective in the absence of IRF8. In Irf8-/- macrophages we observed that clearance of intracellular pathogenic bacteria, Listeria monocytogenes, is impaired. Upon infection, in WT macrophages most of the bacteria were found to be localized within the autophagosomes whereas in Irf8-/- macrophages bacteria were freely dispersed in the cytoplasm; explaining the reason behind poor clearance of bacteria in the latter cells.
