English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Resistance toward current and new classes of anti-tuberculosis (anti-TB) antibiotics are rapidly emerging; thus, innovative therapies focused on host processes, termed host-directed therapies (HDTs), are promising novel approaches for shortening therapy regimens without inducing drug resistance. Development of new TB drugs is lengthy and expensive, and success is not guaranteed; thus, alternatives are needed. Repurposed drugs have already passed Food and Drug Administration (FDA) as well as European Medicines Agency (EMA) safety requirements and may only need to prove efficacy against  Mycobacterium tuberculosis  ( M.tb ). Phosphodiesterases (PDEs) hydrolyze the catalytic breakdown of both cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) to their inactive mononucleotides. Advances in molecular pharmacology have identified 11 PDE families; and the success of sildenafil, a PDE-5 selective inhibitor (PDE-5i), in treating pulmonary hypertension and erectile dysfunction has invigorated research into the therapeutic potential of selective PDE inhibitors in other conditions. Myeloid-derived suppressor cells (MDSCs) suppress anti-TB T-cell responses, likely contributing to TB disease progression. PDE-5i increases cGMP within MDSC resulting in the downregulation of arginase-1 (ARG1) and nitric oxide synthase 2 (NOS2), reducing MDSC's suppressive potential. The effect of this reduction decreases MDSC-induced T-cell-suppressive mechanisms. This review highlights the possibility of HDT targeting of MDSC, using a PDE-5i in combination with the current TB regimen, resulting in improved TB treatment efficacy.

Myeloid-Derived Suppressor Cells as Target of Phosphodiesterase-5 Inhibitors in Host-Directed Therapeutics for Tuberculosis