Sildenafil, a Type-5 Phosphodiesterase Inhibitor, Fails to Reverse Myeloid-Derived Suppressor Cell-Mediated T Cell Suppression in Cells Isolated From Tuberculosis Patients

被引：5

作者：

Leukes, Vinzeigh N. ^{[1
]}

Malherbe, Stephanus T. ^{[1
]}

Hiemstra, Andriette ^{[1
]}

Kotze, Leigh A. ^{[1
]}

Roos, Kelly ^{[1
]}

Keyser, Alana ^{[2
]}

De Swardt, Dalene ^{[3
]}

Gutschmidt, Andrea ^{[1
]}

Walzl, Gerhard ^{[1
]}

du Plessis, Nelita ^{[1
]}

机构：

[1] Stellenbosch Univ, Fac Med & Hlth Sci, DSI NRF Ctr Excellence Biomed TB Res, Div Mol Biol & Human Genet,South African Med Res C, Cape Town, South Africa

[2] Univ Cape Town, Inst Infect Dis & Mol Med, Dept Pathol, Div Med Virol, Cape Town, South Africa

[3] Stellenbosch Univ, Cent Analyt Facil, Cape Town, South Africa

来源：

FRONTIERS IN IMMUNOLOGY | 2022年 / 13卷

基金：

新加坡国家研究基金会; 美国国家卫生研究院;

关键词：

tuberculosis; Mycobacterium tuberculosis; host-directed therapies; myeloid-derived suppressor cells; Sildenafil; URINARY-TRACT SYMPTOMS; PDE5; INHIBITORS; VAGINAL SILDENAFIL; SYSTEMIC-SCLEROSIS; ANTITUMOR IMMUNITY; CITRATE; COMBINATION; DYSFUNCTION; CYTOCHROME-P450; ULCERATIONS;

D O I：

10.3389/fimmu.2022.883886

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Successful TB treatment is hampered by increasing resistance to the two most effective first-line anti-TB drugs, namely isoniazid and rifampicin, thus innovative therapies focused on host processes, termed host-directed therapies (HDTs), are promising novel approaches for increasing treatment efficacy without inducing drug resistance. We assessed the ability of Sildenafil, a type-5 phosphodiesterase inhibitor, as a repurposed compound, to serve as HDT target, by counteracting the suppressive effects of myeloid-derived suppressor cells (MDSC) obtained from active TB cases on T-cell responsiveness. We confirm that MDSC suppress non-specific T-cell activation. We also show that Sildenafil treatment fails to reverse the MDSC-mediated suppression of T-cell functions measured here, namely activation and proliferation. The impact of Sildenafil treatment on improved immunity, using the concentration tested here, is likely to be minimal, but further identification and development of MDSC-targeting TB host-directed therapies are warranted.

引用

页数：11

共 68 条

[11] The Frequency and Effect of Granulocytic Myeloid-Derived Suppressor Cells on Mycobacterial Survival in Patients With Tuberculosis: A Preliminary Report [J].