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Vitamin D status contributes to the antimicrobial activity of macrophages against Mycobacterium leprae.
Kim, Elliot W; Teles, Rosane M B; Haile, Salem; Liu, Philip T; Modlin, Robert L.
Afiliación
  • Kim EW; Molecular Biology Institute, University of California, Los Angeles, Los Angeles, California, United States of America.
  • Teles RMB; Division of Dermatology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, United States of America.
  • Haile S; Department of Hematology and Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California, United States of America.
  • Liu PT; Division of Dermatology, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, California, United States of America.
  • Modlin RL; UCLA and Orthopaedic Hospital Department of Orthopaedic Surgery and the Orthopaedic Hospital Research Center, Los Angeles, Los Angeles, California, United States of America.
PLoS Negl Trop Dis ; 12(7): e0006608, 2018 07.
Article en En | MEDLINE | ID: mdl-29965969
BACKGROUND: The immune system depends on effector pathways to eliminate invading pathogens from the host in vivo. Macrophages (MΦ) of the innate immune system are armed with vitamin D-dependent antimicrobial responses to kill intracellular microbes. However, how the physiological levels of vitamin D during MΦ differentiation affect phenotype and function is unknown. METHODOLOGY/PRINCIPAL: The human innate immune system consists of divergent MΦ subsets that serve distinct functions in vivo. Both IL-15 and IL-10 induce MΦ differentiation, but IL-15 induces primary human monocytes to differentiate into antimicrobial MΦ (IL-15 MΦ) that robustly express the vitamin D pathway. However, how vitamin D status alters IL-15 MΦ phenotype and function is unknown. In this study, we found that adding 25-hydroxyvitamin D3 (25D3) during the IL-15 induced differentiation of monocytes into MΦ increased the expression of the antimicrobial peptide cathelicidin, including both CAMP mRNA and the encoded protein cathelicidin in a dose-dependent manner. The presence of physiological levels of 25D during differentiation of IL-15 MΦ led to a significant vitamin D-dependent antimicrobial response against intracellular Mycobacterium leprae but did not change the phenotype or phagocytic function of these MΦ. These data suggest that activation of the vitamin D pathway during IL-15 MΦ differentiation augments the antimicrobial response against M. leprae infection. CONCLUSIONS/SIGNIFICANCE: Our data demonstrates that the presence of vitamin D during MΦ differentiation bestows the capacity to mount an antimicrobial response against M. leprae.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vitamina D / Lepra / Macrófagos / Mycobacterium leprae Límite: Humans Idioma: En Revista: PLoS Negl Trop Dis Asunto de la revista: MEDICINA TROPICAL Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vitamina D / Lepra / Macrófagos / Mycobacterium leprae Límite: Humans Idioma: En Revista: PLoS Negl Trop Dis Asunto de la revista: MEDICINA TROPICAL Año: 2018 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos