4.6 Article

Reduced vitamin D receptor (VDR) and cathelicidin antimicrobial peptide (CAMP) gene expression contribute to the maintenance of inflammatory immune response in leprosy patients

Journal

MICROBES AND INFECTION
Volume 24, Issue 6-7, Pages -

Publisher

ELSEVIER
DOI: 10.1016/j.micinf.2022.104981

Keywords

Leprosy; Vitamin D receptor; Cathelicidin antimicrobial peptide; Gene expression; Path analysis

Funding

  1. Fundacao de Amparo a Pesquisa do Estado de Minas Gerais (FAPEMIG) [APQ-04035-17, APQ-02871-15, APQ-02332-13]
  2. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq) [104114-19, 303345/2018-7, 485891/2013-1]

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This study focuses on the effects of Vitamin D Receptor (VDR) and Cath-elicidin Antimicrobial Peptide (CAMP) gene expressions on cytokine levels in leprosy patients. The results indicate that the expressions of these genes are strongly correlated with inflammatory responses and persist even after treatment. Vitamin D supplementation is recommended to improve gene expressions in leprosy patients.
Leprosy is an infectious disease influenced by genetic, immunological, and environmental factors. Reduced gene expressions may be associated with the immunological response pattern and leprosy susceptibility. We investigated the direct and indirect effects of Vitamin D Receptor (VDR) and Cath-elicidin Antimicrobial Peptide (CAMP) gene expressions on the serum levels of vitamin D, Cathelicidin, and cytokines in newly-diagnosed leprosy patients and post-six-months of multidrug therapy (MDT). Thirty-four leprosy patients were assessed, paucibacillary (PB; n = 14) and multibacillary (MB; n = 20) cases, untreated or having received six months of MDT, 18 healthy controls, and 25 household contacts. VDR and CAMP gene expression levels were strongly correlated to some important cytokines in both, untreated leprosy patients (PB, r = 0.9319; MB, r = 0.9569) and patients who had undergone MDT (PB, r = 0.9667; MB, r = 0.9569). We observed that both gene expressions directly influenced IL-2, IFN-g, and IL-17F serum levels in leprosy patients compared to the household contacts and healthy individuals. VDR and CAMP gene expressions induced a persistent inflammatory response in PB and MB leprosy patients, even after six months of MDT, to fight the Mycobacterium leprae infection. Due to the persistent in-flammatory profile, multidrug therapy is suggested to be maintained for more than six months, espe-cially for MB patients. Vitamin D supplementation is recommended from the onset as a transcription factor to improve VDR and CAMP gene expression in leprosy patients. (c) 2022 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

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