TY - JOUR
T1 - All trans retinoic acid as a host-directed immunotherapy for tuberculosis
AU - Bahlool, Ahmad Z.
AU - Grant, Conor
AU - Cryan, Sally Ann
AU - Keane, Joseph
AU - O'Sullivan, Mary P.
N1 - Publisher Copyright:
© 2022
PY - 2022/1
Y1 - 2022/1
N2 - Tuberculosis (TB) is the top bacterial infectious disease killer and one of the top ten causes of death worldwide. The emergence of strains of multiple drug-resistant tuberculosis (MDR-TB) has pushed our available stock of anti-TB agents to the limit of effectiveness. This has increased the urgent need to develop novel treatment strategies using currently available resources. An adjunctive, host-directed therapy (HDT) designed to act on the host, instead of the bacteria, by boosting the host immune response through activation of intracellular pathways could be the answer. The integration of multidisciplinary approaches of repurposing currently FDA-approved drugs, with a targeted drug-delivery platform is a very promising option to reduce the long timeline associated with the approval of new drugs - time that cannot be afforded given the current levels of morbidity and mortality associated with TB infection. The deficiency of vitamin A has been reported to be highly associated with the increased susceptibility of TB. All trans retinoic acid (ATRA), the active metabolite of vitamin A, has proven to be very efficacious against TB both in vitro and in vivo. In this review, we discuss and summarise the importance of vitamin A metabolites in the fight against TB and what is known regarding the molecular mechanisms of ATRA as a host-directed therapy for TB including its effect on macrophages cytokine profile and cellular pathways. Furthermore, we focus on the issues behind why previous clinical trials with vitamin A supplementation have failed, and how these issues might be overcome.
AB - Tuberculosis (TB) is the top bacterial infectious disease killer and one of the top ten causes of death worldwide. The emergence of strains of multiple drug-resistant tuberculosis (MDR-TB) has pushed our available stock of anti-TB agents to the limit of effectiveness. This has increased the urgent need to develop novel treatment strategies using currently available resources. An adjunctive, host-directed therapy (HDT) designed to act on the host, instead of the bacteria, by boosting the host immune response through activation of intracellular pathways could be the answer. The integration of multidisciplinary approaches of repurposing currently FDA-approved drugs, with a targeted drug-delivery platform is a very promising option to reduce the long timeline associated with the approval of new drugs - time that cannot be afforded given the current levels of morbidity and mortality associated with TB infection. The deficiency of vitamin A has been reported to be highly associated with the increased susceptibility of TB. All trans retinoic acid (ATRA), the active metabolite of vitamin A, has proven to be very efficacious against TB both in vitro and in vivo. In this review, we discuss and summarise the importance of vitamin A metabolites in the fight against TB and what is known regarding the molecular mechanisms of ATRA as a host-directed therapy for TB including its effect on macrophages cytokine profile and cellular pathways. Furthermore, we focus on the issues behind why previous clinical trials with vitamin A supplementation have failed, and how these issues might be overcome.
KW - Host-directed therapy (HDT)
KW - Macrophage
KW - Retinoic acid (ATRA)
KW - Tuberculosis (TB)
UR - https://www.scopus.com/pages/publications/85132308781
U2 - 10.1016/j.crimmu.2022.03.003
DO - 10.1016/j.crimmu.2022.03.003
M3 - Review article
AN - SCOPUS:85132308781
SN - 2590-2555
VL - 3
SP - 54
EP - 72
JO - Current Research in Immunology
JF - Current Research in Immunology
ER -