Abstract
In this study we explored the role of histone deacetylases (HDACs), a group of epigenetic regulators, in production of type I interferon (IFN) by macrophages and dendritic cells (DCs) in response Mycobacterium tuberculosis (Mtb) infection and Poly I:C, a viral RNA mimic, stimulation. Human monocyte derived macrophages (MDMs) and DCs (MDDCs) stimulated with either Poly I:C or infected with Mtb produced elevated IFN-β and this was inhibited both at the protein and mRNA levels by 4-(dimethyl amino)-N-[6-(hydroxyamino)-6-oxohexyl]-benzamide (DHOB) and CAY10603 (CAY), chemical inhibitors targeting HDAC1. This was further supported by THP1-derived macrophages with HDAC1 knockdown producing reduced IFN-β in response to PMA stimulation or Mtb infection compared to their control cells. Inhibition of HDAC1 with DHOB and CAY reduced phosphorylation of IRF3, a major transcription factor of IFN-β. We conclude that HDAC1 is required for type I IFN production by innate immune cells in response to Mtb infection.
Date of publication
Spring 5-19-2025
Document Type
Thesis
Language
english
Persistent identifier
http://hdl.handle.net/10950/4856
Degree
Master of Science in Biotechnology
Recommended Citation
Omeje, Andy, "ROLE OF HDAC1 IN TYPE I IFN PRODUCTION BY MACROPHAGES AND DENDRITIC CELLS IN RESPONSE TO TLR3 STIMULATION AND MYCOBACTERIUM TUBERCULOSIS INFECTION" (2025). Biotechnology Theses. Paper 27.
http://hdl.handle.net/10950/4856