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Reduced vitamin D-induced cathelicidin production and killing of Mycobacterium tuberculosis in macrophages from a patient with a nonfunctional vitamin D receptor: A case report.

Authors :
Al-Jaberi, Fatima A. H.
Crone, Cornelia Geisler
Lindenstrøm, Thomas
Arildsen, Nicolai Skovbjerg
Lindeløv, Emilia Sæderup
Aagaard, Louise
Gravesen, Eva
Mortensen, Rasmus
Andersen, Aase Bengaard
Olgaard, Klaus
Hjaltelin, Jessica Xin
Brunak, Søren
Menné Bonefeld, Charlotte
Kongsbak-Wismann, Martin
Geisler, Carsten
Source :
Frontiers in Immunology; 11/4/2022, Vol. 13, p1-9, 9p
Publication Year :
2022

Abstract

Tuberculosis (TB) presents a serious health problem with approximately a quarter of the world's population infected with Mycobacterium tuberculosis (M. tuberculosis) in an asymptomatic latent state of which 5-10% develops active TB at some point in their lives. The antimicrobial protein cathelicidin has broad antimicrobial activity towards viruses and bacteria including M. tuberculosis. Vitamin D increases the expression of cathelicidin in many cell types including macrophages, and it has been suggested that the vitamin Dmediated antimicrobial activity against M. tuberculosis is dependent on the induction of cathelicidin. However, unraveling the immunoregulatory effects of vitamin D in humans is hampered by the lack of suitable experimental models. We have previously described a family in which members suffer from hereditary vitamin D-resistant rickets (HVDRR). The family carry a mutation in the DNAbinding domain of the vitamin D receptor (VDR). This mutation leads to a nonfunctional VDR, meaning that vitamin D cannot exert its effect in family members homozygous for the mutation. Studies of HVDRR patients open unique possibilities to gain insight in the immunoregulatory roles of vitamin D in humans. Here we describe the impaired ability of macrophages to produce cathelicidin in a HVDRR patient, who in her adolescence suffered from extrapulmonary TB. The present case is a rare experiment of nature, which illustrates the importance of vitamin D in the pathophysiology of combating M. tuberculosis. [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
16643224
Volume :
13
Database :
Complementary Index
Journal :
Frontiers in Immunology
Publication Type :
Academic Journal
Accession number :
160321421
Full Text :
https://doi.org/10.3389/fimmu.2022.1038960