High Vitamin D Concentrations Restore the Ability to Express LL37 by M. tuberculosis-Infected Human Macrophages
Por:
Herrera, Maria Teresa, Juarez, Esmeralda, Guzman-Beltran, Silvia, Torres, Martha, Luna-Morales, Victor Adrian, Villalana-Alvarez, Leonardo Daniel, Gonzalez, Yolanda
Publicada:
1 feb 2022
Resumen:
Vitamin D has an immunomodulatory function and is involved in
eliminating pathogens. Vitamin D deficiencies reported in Type 2
diabetes mellitus (T2DM) patients make them more susceptible to
developing tuberculosis (TB). The macrophages are the immune cells that
control intracellular pathogens by producing the antimicrobial peptide
cathelicidin-LL37. This pathway involves TLR activation by pathogens,
vitamin D receptor (VDR) ligation, and the enzyme 1 alpha-hydroxylase
Cytochrome P450 Family 27 Subfamily B Member 1 (CYP27B1). However, it is
not clear whether the biological actions of vitamin D are affected by
high glucose concentrations. This study aimed to evaluate the vitamin D
contribution in the expression of VDR and CYP27B1, involved in the
conversion of an inactive to an active form of vitamin D in the infected
macrophages using M. tuberculosis as an infection model. The expression
of LL37 and the nucleus translocation of VDR were evaluated as the
readout of the response of vitamin D and determined if those processes
are affected by glucose concentrations. Macrophages from healthy donors
were cultured under glucose concentrations of 5.5, 15, or 30 mM,
stimulated with vitamin D in inactive (25(OH)D-3) or active
(1,25(OH)(2)D-3) forms, and infected with M. tuberculosis. The vitamin
D-dependent induction of LL37 and the expression of VDR and CYP27B1
genes were analyzed by qPCR, and VDR translocation was analyzed in
nuclear protein extracts by ELISA. M. tuberculosis downregulated the
expression of LL37 regardless of the glucose concentration, whereas VDR
and CYP27B1 upregulated it regardless of the glucose concentration.
After evaluating two concentrations of vitamin D, 1 nM or 1 mu M, the
high concentration (1 mu M) was necessary to restore the induction of
LL37 expression in M. tuberculosis-infected macrophages. High
concentrations of the inactive form of vitamin D restore the infected
macrophages' ability to express LL37 regardless of the glucose
concentration. This finding supports the idea that vitamin D
administration in patients with T2DM could benefit TB control and
prevention.
Filiaciones:
Herrera, Maria Teresa:
Department of Microbiology Research, National Institute for Respiratory Diseases, Ismael Cosío Villegas, Mexico City, CP 14080, Mexico
Juarez, Esmeralda:
Department of Microbiology Research, National Institute for Respiratory Diseases, Ismael Cosío Villegas, Mexico City, CP 14080, Mexico
Guzman-Beltran, Silvia:
Department of Microbiology Research, National Institute for Respiratory Diseases, Ismael Cosío Villegas, Mexico City, CP 14080, Mexico
Torres, Martha:
Biomedical Research Sub Direction, National Institute for Respiratory Diseases, Ismael Cosío Villegas, Mexico City, CP 14080, Mexico
Luna-Morales, Victor Adrian:
Facultad de Ciencias, Universidad Nacional Autónoma de México, Mexico City, CP 14080, Mexico
Villalana-Alvarez, Leonardo Daniel:
Facultad de Ciencias, Universidad Nacional Autónoma de México, Mexico City, CP 14080, Mexico
Gonzalez, Yolanda:
Department of Microbiology Research, National Institute for Respiratory Diseases, Ismael Cosío Villegas, Mexico City, CP 14080, Mexico
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