Hostname: page-component-8448b6f56d-sxzjt Total loading time: 0 Render date: 2024-04-24T09:51:47.065Z Has data issue: false hasContentIssue false
  • English
  • Français

Vitamin D increases killing of intracellular Leishmania amazonensis in vitro independently of macrophage oxidative mechanisms

Published online by Cambridge University Press:  22 September 2020

Patrícia de Almeida Machado ,
Douglas Oliveira Escrivani ,
Daniel Claudio Oliveira Gomes Open the ORCID record for Daniel Claudio Oliveira Gomes [Opens in a new window] ,
Bartira Rossi-Bergmann ,
Suzana Passos Chaves ,
Elaine Soares Coimbra  and
Herbert Leonel de Matos Guedes Open the ORCID record for Herbert Leonel de Matos Guedes [Opens in a new window]
Patrícia de Almeida Machado
Affiliation:
Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, RJ, Brazil Departamento de Parasitologia, Microbiologia e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brazil
Douglas Oliveira Escrivani
Affiliation:
Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
Daniel Claudio Oliveira Gomes
Affiliation:
Núcleo de Doenças Infecciosas/Núcleo de Biotecnologia – Universidade Federal do Espírito Santo, Vitória, ES, Brazil
Bartira Rossi-Bergmann
Affiliation:
Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
Suzana Passos Chaves
Affiliation:
Laboratório de Imunoparasitologia, Universidade Federal do Rio de Janeiro Campus Macaé, RJ, Brazil
Elaine Soares Coimbra*
Affiliation:
Departamento de Parasitologia, Microbiologia e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brazil
Herbert Leonel de Matos Guedes*
Affiliation:
Laboratório de Imunofarmacologia, Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil Laboratório Interdisciplinar de Pesquisas Médicas, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, RJ, Brazil UFRJ Campus Duque de Caxias Professor Geraldo Cidade – Universidade Federal do Rio de Janeiro, Duque de Caxias, Rio de Janeiro, RJ, Brazil
*
Author for correspondence: Elaine Soares Coimbra, E-mail: elaine.coimbra@ufjf.edu.br, Herbert Leonel de Matos Guedes, E-mail: herbert@biof.ufrj.br, herbert@ioc.fiocruz.br
Author for correspondence: Elaine Soares Coimbra, E-mail: elaine.coimbra@ufjf.edu.br, Herbert Leonel de Matos Guedes, E-mail: herbert@biof.ufrj.br, herbert@ioc.fiocruz.br
Get access Rights & Permissions [Opens in a new window]

Abstract

Vitamin D has been reported to activate macrophage microbicidal mechanisms by inducing the production of antimicrobial peptides and nitric oxide (NO), but conversely has been shown to contribute to a greater susceptibility to Leishmania amazonensis infection in mice. Thus, this study aimed to evaluate the role of vitamin D during intracellular infection with L. amazonensis by examining its effect on macrophage oxidative mechanisms and parasite survival in vitro. Vitamins D2 and D3 significantly inhibited promastigote and amastigote growth in vitro. Vitamin D3 was not able to induce NO and reactive oxygen species (ROS) production in uninfected macrophages or macrophages infected with L. amazonensis. In addition, vitamin D3 in combination with interferon (IFN)-γ did not enhance amastigote killing and in fact, significantly reduced NO and ROS production when compared with the effect of IFN-γ alone. In this study, we demonstrated that vitamin D directly reduces parasite growth in infected macrophages (approximately 50–60% at 50 μm) but this effect is independent of the activation of macrophage oxidative mechanisms. These findings will contribute to a better understanding of the role of vitamin D in cutaneous leishmaniasis.

Keywords

Leishmania amazonensismacrophagesNOROSVitamin D
Type
Research Article
Information
Parasitology , Volume 147 , Issue 14 , December 2020 , pp. 1792 - 1800
Check for updates
Copyright
Copyright © The Author(s), 2020. Published by Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Anversa, L, Tiburcio, MGS, Richini-Pereira, VB, Ramirez, LE, Anversa, L, Tiburcio, MGS, Richini-Pereira, VB and Ramirez, LE (2018) Human leishmaniasis in Brazil: a general review. Revista da Associação Médica Brasileira 64, 281–289.10.1590/1806-9282.64.03.281CrossRefGoogle ScholarPubMed
Aronson, NE and Joya, CA (2019) Cutaneous leishmaniasis updates in diagnosis and management. Infectious Disease Clinics of NA 33, 101–117.Google ScholarPubMed
Bacchetta, J, Chun, RF, Gales, B, Zaritsky, JJ, Leroy, S, Wesseling-Perry, K, Boregaard, N, Rastogi, A, Salusky, IB and Hewison, M (2014) Antibacterial responses by peritoneal macrophages are enhanced following vitamin D supplementation. PLoS One 9, e116530.10.1371/journal.pone.0116530CrossRefGoogle ScholarPubMed
Bendik, I, Friedel, A, Roos, FF, Weber, P and Eggersdorfer, M (2014) Vitamin D: a critical and essential micronutrient for human health. Frontiers in Physiology 5, 1–14. doi:10.3389/fphys.2014.00248.CrossRefGoogle ScholarPubMed
Bezerra, IPdS, Oliveira-Silva, G, Braga, DSFS, de Mello, MF, Pratti, JES, Pereira, JC, da Fonseca-Martins, AM, Firmino-Cruz, L, Maciel-Oliveira, D, Ramos, TD, Vale, AM, Gomes, DCO, Rossi-Bergmann, B and de Matos Guedes, HL (2019) Dietary vitamin D3 deficiency increases resistance to Leishmania (Leishmania) amazonensis infection in mice. Frontiers in Cellular and Infection Microbiology 9, 88.10.3389/fcimb.2019.00088CrossRefGoogle ScholarPubMed
Carlsen, ED, Liang, Y, Shelite, TR, Walker, DH, Melby, PC and Soong, L (2015) Permissive and protective roles for neutrophils in leishmaniasis. Clinical and Experimental Immunology 182, 109–118.10.1111/cei.12674CrossRefGoogle ScholarPubMed
Chen, S, Sims, GP, Chen, XX, Gu, YY, Chen, S and Lipsky, PE (2007) Modulatory effects of 1,25-dihydroxyvitamin D3 on human B cell differentiation. The Journal of Immunology 179, 1634–1647.10.4049/jimmunol.179.3.1634CrossRefGoogle ScholarPubMed
Custodio, E, Herrero, M, Bouza, C, López-Alcalde, J, Benito, A and Alvar, J (2016) Nutritional supplements for patients being treated for active visceral leishmaniasis. Cochrane Database of Systematic Reviews 6, Art. No.: CD012261. doi: 10.1002/14651858.CD012261.Google Scholar
Ehrchen, J, Helming, L, Varga, G, Pasche, B, Loser, K, Gunzer, M, Sunderkötter, C, Sorg, C, Roth, J and Lengeling, A (2007) Vitamin D receptor signaling contributes to susceptibility to infection with Leishmania major. The FASEB Journal 21, 3208–3218.10.1096/fj.06-7261comCrossRefGoogle ScholarPubMed
Fabri, M, Stenger, S, Shin, D-M, Yuk, J-M, Liu, PT, Realegeno, S, Lee, H-M, Krutzik, SR, Schenk, M, Sieling, PA, Teles, R, Montoya, D, Iyer, SS, Bruns, H, Lewinsohn, DM, Hollis, BW, Hewison, M, Adams, JS, Steinmeyer, A, Zugel, U, Cheng, G, Jo, E-K, Bloom, BR and Modlin, RL (2011) Vitamin D is required for IFN-mediated antimicrobial activity of human macrophages. Science Translational Medicine 3, 104ra102–104ra102.10.1126/scitranslmed.3003045CrossRefGoogle Scholar
García-Barragán, Á, Gutiérrez-Pabello, JA and Alfonseca-Silva, E (2018) Calcitriol increases nitric oxide production and modulates microbicidal capacity against Mycobacterium bovis in bovine macrophages. Comparative Immunology, Microbiology and Infectious Diseases 59, 17–23.10.1016/j.cimid.2018.09.001CrossRefGoogle ScholarPubMed
Gough, ME, Graviss, EA and May, EE (2017) The dynamic immunomodulatory effects of vitamin D3 during Mycobacterium infection. Innate Immunity 23, 506–523.10.1177/1753425917719143CrossRefGoogle ScholarPubMed
Green, LC, Wagner, DA, Glogowski, J, Skipper, PL, Wishnok, JS and Tannenbaum, SR (1982) Analysis of nitrate, nitrite, and [15N]nitrate in biological fluids. Analytical Biochemistry 126, 131–138.10.1016/0003-2697(82)90118-XCrossRefGoogle Scholar
Greenstein, RJ, Su, L and Brown, ST (2012) Vitamins A & D inhibit the growth of mycobacteria in radiometric culture. PLoS One 7, e29631.10.1371/journal.pone.0029631CrossRefGoogle ScholarPubMed
Hart, PH, Gorman, S and Finlay-Jones, JJ (2011) Modulation of the immune system by UV radiation: more than just the effects of vitamin D? Nature Reviews Immunology 11, 584–596.10.1038/nri3045CrossRefGoogle ScholarPubMed
Heikkinen, S, Väisänen, S, Pehkonen, P, Seuter, S, Benes, V and Carlberg, C (2011) Nuclear hormone 1α,25-dihydroxyvitamin D3 elicits a genome-wide shift in the locations of VDR chromatin occupancy. Nucleic Acids Research 39, 9181–9193.10.1093/nar/gkr654CrossRefGoogle ScholarPubMed
Helming, L, Böse, J, Ehrchen, J, Schiebe, S, Frahm, T, Geffers, R, Probst-Kepper, M, Balling, R and Lengeling, A (2005) 1,25-Dihydroxyvitamin D3 is a potent suppressor of interferon -mediated macrophage activation. Blood 106, 4351–4358.10.1182/blood-2005-03-1029CrossRefGoogle ScholarPubMed
Henard, CA, Carlsen, ED, Hay, C, Kima, PE and Soong, L (2014) Leishmania amazonensis amastigotes highly express a tryparedoxin peroxidase isoform that increases parasite resistance to macrophage antimicrobial defenses and fosters parasite virulence. PLoS Neglected Tropical Diseases 8, e3000.10.1371/journal.pntd.0003000CrossRefGoogle ScholarPubMed
Hoare, CA and Wallace, FG (1966) Developmental stages of trypanosomatid flagellates: a new terminology. Nature 212, 1385–1386.10.1038/2121385a0CrossRefGoogle Scholar
Holick, MF (2008) Sunlight, UV-radiation, vitamin D and skin cancer: how much sunlight do we need?. In Reichrath, J (ed.), Sunlight, Vitamin D and Skin Cancer. New York, New York, NY: Springer, pp. 1–15. 10.1007/978-0-387-77574-6_1.Google ScholarPubMed
Hollis, BW and Wagner, CL (2013) Clinical review: the role of the parent compound vitamin D with respect to metabolism and function: why clinical dose intervals can affect clinical outcomes. The Journal of Clinical Endocrinology and Metabolism 98, 4619–4628.10.1210/jc.2013-2653CrossRefGoogle ScholarPubMed
Huang, B, Yan, S, Chen, C and Ye, S (2019) Effect of 25-hydroxyvitamin D on Helicobacter pylori eradication in patients with type 2 diabetes. Wiener klinische Wochenschrift 131, 75–80.10.1007/s00508-018-1416-yCrossRefGoogle ScholarPubMed
Jo, E-K (2010) Innate immunity to mycobacteria: vitamin D and autophagy. Cellular Microbiology 12, 1026–1035.CrossRefGoogle ScholarPubMed
Kaye, P and Scott, P (2011) Leishmaniasis: complexity at the host–pathogen interface. Nature Reviews Microbiology 9, 604–615.Google ScholarPubMed
Kim, EW, Teles, RMB, Haile, S, Liu, PT and Modlin, RL (2018) Vitamin D status contributes to the antimicrobial activity of macrophages against Mycobacterium leprae. PLoS Neglected Tropical Diseases 12, e0006608.10.1371/journal.pntd.0006608CrossRefGoogle ScholarPubMed
Kima, PE (2014) Leishmania molecules that mediate intracellular pathogenesis. Microbes and Infection 16, 721–726.10.1016/j.micinf.2014.07.012CrossRefGoogle ScholarPubMed
Kościuczuk, EM, Lisowski, P, Jarczak, J, Strzałkowska, N, Jóźwik, A, Horbańczuk, J, Krzyżewski, J, Zwierzchowski, L and Bagnicka, E (2012) Cathelicidins: family of antimicrobial peptides. A review. Molecular Biology Reports 39, 10957–10970.10.1007/s11033-012-1997-xCrossRefGoogle ScholarPubMed
Lemire, JM, Adams, JS, Kermani-Arab, V, Bakke, AC, Sakai, R and Jordan, SC (1985) 1,25-Dihydroxyvitamin D3 suppresses human T helper/inducer lymphocyte activity in vitro. Journal of immunology (Baltimore, MD.: 1950) 134, 3032–3035.Google Scholar
Losada-Barragán, M, Umaña-Pérez, A, Cuervo-Escobar, S, Berbert, LR, Porrozzi, R, Morgado, FN, Mendes-da-Cruz, DA, Savino, W, Sánchez-Gómez, M and Cuervo, P (2017) Protein malnutrition promotes dysregulation of molecules involved in T cell migration in the thymus of mice infected with Leishmania infantum. Scientific Reports 7, 45991.CrossRefGoogle Scholar
Marr, AK, Cen, S, Hancock, REW and McMaster, WR (2016) Identification of synthetic and natural host defense peptides with leishmanicidal activity. Antimicrobial Agents and Chemotherapy 60, 2484–2491.10.1128/AAC.02328-15CrossRefGoogle ScholarPubMed
Maxfield, L and Crane, JS (2020) Leishmaniasis. StatPearls Publishing. http://www.ncbi.nlm.nih.gov/pubmed/30285351.Google ScholarPubMed
Prietl, B, Treiber, G, Pieber, TR and Amrein, K (2013) Vitamin D and immune function. Nutrients 5, 2502–2521.Google ScholarPubMed
Qi, H, Ji, J, Wanasen, N and Soong, L (2004) Enhanced replication of Leishmania amazonensis amastigotes in gamma interferon-stimulated murine macrophages: implications for the pathogenesis of cutaneous leishmaniasis. Infection and Immunity 72, 988–995.10.1128/IAI.72.2.988-995.2004CrossRefGoogle ScholarPubMed
Ramos-Martínez, E, Villaseñor-Cardoso, MI, López-Vancell, MR, García-Vázquez, FJ, Pérez-Torres, A, Salaiza-Suazo, N and Pérez-Tamayo, R (2013) Effect of 1,25(OH)2D3 on BALB/c mice infected with Leishmania mexicana. Experimental Parasitology 134, 413–421.10.1016/j.exppara.2013.05.009CrossRefGoogle ScholarPubMed
Ramos-Martínez, E, Gutierrez-Kobeh, L and Villaseñor-Cardoso, MI (2015) The role of vitamin D in the control of Leishmania infection. Canadian Journal of Physiology and Pharmacology 93, 369–376.Google ScholarPubMed
Rivas-Santiago, B, Hernandez-Pando, R, Carranza, C, Juarez, E, Contreras, JL, Aguilar-Leon, D, Torres, M and Sada, E (2008) Expression of cathelicidin LL-37 during Mycobacterium tuberculosis infection in human alveolar macrophages, monocytes, neutrophils, and epithelial cells. Infection and Immunity 76, 935–941.10.1128/IAI.01218-07CrossRefGoogle ScholarPubMed
Rodriguez-Cortes, A, Martori, C, Martinez-Florez, A, Clop, A, Amills, M, Kubejko, J, Llull, J, Nadal, JM and Alberola, J (2017) Canine leishmaniasis progression is associated with vitamin D deficiency. Scientific Reports 7, 3346.Google ScholarPubMed
Rook, GA, Steele, J, Fraher, L, Barker, S, Karmali, R, O'Riordan, J and Stanford, J (1986) Vitamin D3, gamma interferon, and control of proliferation of Mycobacterium tuberculosis by human monocytes. Immunology 57, 159–163.Google ScholarPubMed
Santos, CS and Brodskyn, CI (2014) The role of CD4 and CD8T cells in human cutaneous leishmaniasis. Frontiers in Public Health 2, 1–6.Google Scholar
van Griensven, J and Diro, E (2019) Visceral Leishmaniasis: recent advances in diagnostics and treatment regimens. Infectious Disease Clinics of North America 33, 79–99.10.1016/j.idc.2018.10.005CrossRefGoogle ScholarPubMed
Vanherwegen, A-S, Gysemans, C and Mathieu, C (2017) Vitamin D endocrinology on the cross-road between immunity and metabolism. Molecular and Cellular Endocrinology 453, 52–67.CrossRefGoogle ScholarPubMed
Waters, WR, Nonnecke, BJ, Rahner, TE, Palmer, MV, Whipple, DL and Horst, RL (2001) Modulation of Mycobacterium bovis-specific responses of bovine peripheral blood mononuclear cells by 1,25-dihydroxyvitamin D3. Clinical and Vaccine Immunology 8, 1204–1212.Google Scholar
Whitcomb, JP, DeAgostino, M, Ballentine, M, Fu, J, Tenniswood, M, Welsh, J, Cantorna, M and McDowell, MA (2012) The role of vitamin D and vitamin D receptor in immunity to Leishmania major infection. Journal of Parasitology Research 2012, 1–10.Google ScholarPubMed
World Health Organization (2019) Leishmaniasis. World Health Organization. https://www.who.int/en/news-room/fact-sheets/detail/leishmaniasis#Google Scholar
Xu, H, Soruri, A, Gieseler, RKH and Peters, JH (1993) 1,25-Dihydroxyvitamin D3 exerts opposing effects to IL-4 on MHC class-II antigen expression, accessory activity, and phagocytosis of human monocytes. Scandinavian Journal of Immunology 38, 535–540.10.1111/j.1365-3083.1993.tb03237.xCrossRefGoogle ScholarPubMed
Yamamoto, K, Iwagami, M, Seki, T, Kano, S, Ota, N and Ato, M (2017) Dual antiplasmodial activity of vitamin D3 and its analog, 22-oxacalcitriol, by direct and indirect mechanisms. Parasitology International 66, 89–99.10.1016/j.parint.2016.11.015CrossRefGoogle ScholarPubMed
Yamamoto, K, Takahashi, K, Ato, M, Iwanaga, S and Ohta, N (2019) Antimalarial activity of vitamin D3 (VD3) does not result from VD3-induced antimicrobial agents including nitric oxide or cathelicidin. Experimental Parasitology 201, 67-77. doi:10.1016/J.EXPPARA.2019.03.005.CrossRefGoogle ScholarPubMed
Supplementary material: Image

Machado et al. supplementary material

Machado et al. supplementary material 1

Download Machado et al. supplementary material(Image)
Image 2.4 MB
Supplementary material: Image

Machado et al. supplementary material

Machado et al. supplementary material 2

Download Machado et al. supplementary material(Image)
Image 4.3 MB
Supplementary material: Image

Machado et al. supplementary material

Machado et al. supplementary material 3

Download Machado et al. supplementary material(Image)
Image 2.4 MB