Journal
JOURNAL OF LEUKOCYTE BIOLOGY
Volume 110, Issue 1, Pages 177-186Publisher
OXFORD UNIV PRESS
DOI: 10.1002/JLB.4A0720-409RR
Keywords
Mycobacteria; M‐ MDSC; cyclooxygenase‐ 2 inhibitor; host directed therapy; innate immunity
Categories
Funding
- Research Council of Norway (GlobVac) [234493]
- South Eastern Norway Regional Health Authority
- Oslo University Hospital
- University of Oslo
- Stellenbosch University
- European & Developing Countries Clinical Trials Partnership (EDCTP) [CDF1546]
Ask authors/readers for more resources
The study found that cyclooxygenase-2 inhibitors can decrease the expression of monocytic MDSCs in the blood of tuberculosis patients, and reduce the production of specific immune regulatory factors in these cells. Additionally, cyclooxygenase-2 inhibitors also have an impact on mycobacterial infection and the function of monocytic MDSCs.
Myeloid-derived suppressor cells (MDSCs) increase in tuberculosis (TB) and may be targets for host-directed therapy (HDT). In this study, we use flow cytometry to analyze the effects of cyclooxygenase-2 inhibitors (COX-2i) on monocytic (M)-MDSCs in blood from TB patients attending a clinical trial of COX-2i. The effects of COX-2i on M-MDSCs and mycobacterial uptake were also studied by an in vitro mycobacterial infection model. We found that M-MDSC frequencies correlated with TB disease severity. Reduced M-MDSC (P = 0.05) and IDO (P = 0.03) expression was observed in the COX-2i group. We show that peripheral blood-derived M-MDSCs successfully internalized Mycobacterium bovis and that in vitro mycobacterial infection increased COX-2 (P = 0.002), PD-L1 (P = 0.01), and Arginase-1 (P = 0.002) expression in M-MDSCs. Soluble IL-1 beta, IL-10, and S100A9 were reduced in COX-2i-treated M-MDSCs cultures (P < 0.05). We show novel data that COX-2i had limited effect in vivo but reduced M-MDSC cytokine production in vitro. The relevance of COX-2i in a HDT strategy needs to be further explored.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available