TY - JOUR

T1 - Reduced vitamin D-induced cathelicidin production and killing of Mycobacterium tuberculosis in macrophages from a patient with a non-functional vitamin D receptor

T2 - A case report

AU - Al-Jaberi, Fatima A.H.

AU - Crone, Cornelia Geisler

AU - Lindenstrøm, Thomas

AU - Arildsen, Nicolai Skovbjerg

AU - Lindeløv, Emilia Sæderup

AU - Aagaard, Louise

AU - Gravesen, Eva

AU - Mortensen, Rasmus

AU - Andersen, Aase Bengaard

AU - Olgaard, Klaus

AU - Hjaltelin, Jessica Xin

AU - Brunak, Søren

AU - Bonefeld, Charlotte Menné

AU - Kongsbak-Wismann, Martin

AU - Geisler, Carsten

N1 - Publisher Copyright: Copyright © 2022 Al-Jaberi, Crone, Lindenstrøm, Arildsen, Lindeløv, Aagaard, Gravesen, Mortensen, Andersen, Olgaard, Hjaltelin, Brunak, Bonefeld, Kongsbak-Wismann and Geisler.

PY - 2022

Y1 - 2022

N2 - 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 D-mediated 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 DNA-binding domain of the vitamin D receptor (VDR). This mutation leads to a non-functional 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.

AB - 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 D-mediated 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 DNA-binding domain of the vitamin D receptor (VDR). This mutation leads to a non-functional 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.

KW - cathelicidin

KW - hereditary vitamin D-resistant rickets (HVDRR)

KW - macrophage

KW - tuberculosis

KW - vitamin D

U2 - 10.3389/fimmu.2022.1038960

DO - 10.3389/fimmu.2022.1038960

M3 - Journal article

C2 - 36405761

AN - SCOPUS:85142167842

VL - 13

JO - Frontiers in Immunology

JF - Frontiers in Immunology

SN - 1664-3224

M1 - 1038960

ER -