Responses of activated THP-1 cells to Mycobacterium tuberculosis infection during isoniazid and rifampicin in vitro
Keywords:
THP-1 cells, Mycobacterium tuberculosis, isoniazid, rifampicin, comparative proteomic, GeLC MS/MS.Abstract
Background and Objective: Macrophages are cells that play a key role in both innate and adaptive immune responses to TB. Anti-TB drugs might affect the interaction between macrophages and Mycobacterium tuberculosis (Mtb). However, as of yet there have been no studies that reporting on the interaction between Mtb and macrophages during anti-TB treatment. This study aims to study the response of activated THP-1 cells to Mtb infections during isoniazid and rifampicin treatments in vitro.
Methods: The activated THP-1 cell line was cultured and infected with Mtb and was subsequently treated with isoniazid and rifampicin. A culture of uninfected cells as also treated using the same method. Comparative proteomic analysis using GeLC MS/MS was performed. The protein networks were analyzed based on KEGG pathway using Ingenuity software.
Results: Overall, this study found 4,173 proteins, 98 of which were found exclusively in the infected cells and 74 of which were found only in the uninfected cells. The proteins that were expressed in the infected cells were associated with T cell activation (IL2 and CD28), apoptosis (CASP3 and TGFB1), cell survival (NFkB and Akt) and transcriptional regulation (Myc and BCL6). The proteins that were suppressed in the infected cells associated with immune response (IL17A), cell proliferation and survival (ERK and Myc), cell growth and migration (TP53, CTNNB1 and Axin1).
Conclusion: Our study provides information regarding the activated THP-1 cell response to Mtb infection during anti-TB drug treatment in vitro.
