Low Serum Vitamin D Levels in Type 2 Diabetes Patients Are Associated with Decreased Mycobacterial Activity

Overview

Journal BMC Infect Dis

Publisher Biomed Central

Specialty Infectious Diseases

Date 2017 Sep 9

PMID 28882103

Citations 6

Authors

Maria Teresa Herrera

Yolanda Gonzalez

Fernando Hernandez-Sanchez

Guadalupe Fabian-San Miguel

Martha Torres

Affiliations

Soon will be listed here.

Abstract

Background: Concurrent diabetes mellitus and tuberculosis represent a significant health problem worldwide. Patients with diabetes mellitus have a high risk of tuberculosis, which may be mediated by an abnormal innate immune response due to hyperglycaemia or low vitamin D levels.

Methods: In the present study, we evaluated inactive vitamin D serum levels and the monocyte response to infection with M. tuberculosis, including phagocytosis of M. tuberculosis, antimycobacterial activity, LL-37, human β defensin-2 and IL-10 gene expression and nitric oxide production, between type 2 diabetes mellitus patients (n = 51) and healthy volunteers (n = 38).

Results: Twenty-seven type 2 diabetes mellitus patients had inadequate inactive vitamin D levels (<50 nM). The percentages of M. tuberculosis phagocytosis between monocytes were similar across groups according to microscopy. Intracellular mycobacterial growth was similar in infected monocytes from both groups. However, M. tuberculosis growth was significantly higher in monocytes obtained from type 2 diabetes mellitus patients and lower vitamin D levels after 1-h (D0) and 72-h (D3) post-infection (p ≤ 0.05). LL-37, human β defensin-2 and IL-10 mRNA expression were similar between monocytes across groups; vitamin D serum levels and LL-37, human β defensin-2 and IL-10 expression were not correlated. Nitric oxide production was significantly higher in healthy volunteers than in type 2 diabetes mellitus patients with low vitamin D serum levels at D3 post-infection (p ≤ 0.05).

Conclusions: Our results show that monocytes from type 2 diabetes mellitus patients and low vitamin D serum levels show an impaired ability to control the intracellular growth of M. tuberculosis, which is not associated with significant decrease of LL-37 or human β defensin-2 expression. Vitamin D could be the link between diabetes and tuberculosis susceptibility.

Citing Articles

Differential Role of Type 2 Diabetes as a Risk Factor for Tuberculosis in the Elderly versus Younger Adults.

Restrepo B, Scordo J, Aguillon-Duran G, Ayala D, Quirino-Cerrillo A, Loera-Salazar R Pathogens. 2022; 11(12).

PMID: 36558885 PMC: 9784720. DOI: 10.3390/pathogens11121551.

High Vitamin D Concentrations Restore the Ability to Express LL37 by -Infected Human Macrophages.

Herrera M, Juarez E, Guzman-Beltran S, Torres M, Luna-Morales V, Villalana-Alvarez L Biomolecules. 2022; 12(2).

PMID: 35204769 PMC: 8961537. DOI: 10.3390/biom12020268.

Metformin partially reverses the inhibitory effect of co-culture with ER-/PR-/HER2+ breast cancer cells on biomarkers of monocyte antitumor activity.

Dahmani Z, Addou-Klouche L, Gizard F, Dahou S, Messaoud A, Chahinez Djebri N PLoS One. 2020; 15(10):e0240982.

PMID: 33108409 PMC: 7591052. DOI: 10.1371/journal.pone.0240982.

Type 2 Diabetes Mellitus and Altered Immune System Leading to Susceptibility to Pathogens, Especially .

Ferlita S, Yegiazaryan A, Noori N, Lal G, Nguyen T, To K J Clin Med. 2020; 8(12).

PMID: 31888124 PMC: 6947370. DOI: 10.3390/jcm8122219.

Changes in Host Response to Infection Associated With Type 2 Diabetes: Beyond Hyperglycemia.

Segura-Cerda C, Lopez-Romero W, Flores-Valdez M Front Cell Infect Microbiol. 2019; 9:342.

PMID: 31637222 PMC: 6787561. DOI: 10.3389/fcimb.2019.00342.

References

Selvaraj P, Chandra G, Jawahar M, Rani M, Rajeshwari D, Narayanan P . Regulatory role of vitamin D receptor gene variants of Bsm I, Apa I, Taq I, and Fok I polymorphisms on macrophage phagocytosis and lymphoproliferative response to mycobacterium tuberculosis antigen in pulmonary tuberculosis. J Clin Immunol. 2004; 24(5):523-32. DOI: 10.1023/B:JOCI.0000040923.07879.31. View

Takiishi T, Gysemans C, Bouillon R, Mathieu C . Vitamin D and diabetes. Endocrinol Metab Clin North Am. 2010; 39(2):419-46, table of contents. DOI: 10.1016/j.ecl.2010.02.013. View

Zhang Y, Leung D, Richers B, Liu Y, Remigio L, Riches D . Vitamin D inhibits monocyte/macrophage proinflammatory cytokine production by targeting MAPK phosphatase-1. J Immunol. 2012; 188(5):2127-35. PMC: 3368346. DOI: 10.4049/jimmunol.1102412. View

Liu P, Stenger S, Tang D, Modlin R . Cutting edge: vitamin D-mediated human antimicrobial activity against Mycobacterium tuberculosis is dependent on the induction of cathelicidin. J Immunol. 2007; 179(4):2060-3. DOI: 10.4049/jimmunol.179.4.2060. View

de Castro Kroner J, Sommer A, Fabri M . Vitamin D every day to keep the infection away?. Nutrients. 2015; 7(6):4170-88. PMC: 4488779. DOI: 10.3390/nu7064170. View

Liu P, Stenger S, Li H, Wenzel L, Tan B, Krutzik S . Toll-like receptor triggering of a vitamin D-mediated human antimicrobial response. Science. 2006; 311(5768):1770-3. DOI: 10.1126/science.1123933. View

Dimitrov V, White J . Species-specific regulation of innate immunity by vitamin D signaling. J Steroid Biochem Mol Biol. 2015; 164:246-253. DOI: 10.1016/j.jsbmb.2015.09.016. View

Mateen S, Moin S, Shahzad S, Khan A . Level of inflammatory cytokines in rheumatoid arthritis patients: Correlation with 25-hydroxy vitamin D and reactive oxygen species. PLoS One. 2017; 12(6):e0178879. PMC: 5464597. DOI: 10.1371/journal.pone.0178879. View

Arnedo-Pena A, Juan-Cerdan J, Romeu-Garcia A, Garcia-Ferrer D, Holguin-Gomez R, Iborra-Millet J . Vitamin D status and incidence of tuberculosis among contacts of pulmonary tuberculosis patients. Int J Tuberc Lung Dis. 2014; 19(1):65-9. DOI: 10.5588/ijtld.14.0348. View

10.

Fitch N, Becker A, HayGlass K . Vitamin D [1,25(OH)2D3] Differentially Regulates Human Innate Cytokine Responses to Bacterial versus Viral Pattern Recognition Receptor Stimuli. J Immunol. 2016; 196(7):2965-72. DOI: 10.4049/jimmunol.1500460. View

11.

Vieth R . Why "Vitamin D" is not a hormone, and not a synonym for 1,25-dihydroxy-vitamin D, its analogs or deltanoids. J Steroid Biochem Mol Biol. 2004; 89-90(1-5):571-3. DOI: 10.1016/j.jsbmb.2004.03.037. View

12.

Boyum A . Isolation of lymphocytes, granulocytes and macrophages. Scand J Immunol. 1976; Suppl 5:9-15. View

13.

Wei R, Christakos S . Mechanisms Underlying the Regulation of Innate and Adaptive Immunity by Vitamin D. Nutrients. 2015; 7(10):8251-60. PMC: 4632412. DOI: 10.3390/nu7105392. View

14.

Schulz K, Kerber S, Kelm M . Reevaluation of the Griess method for determining NO/NO2- in aqueous and protein-containing samples. Nitric Oxide. 1999; 3(3):225-34. DOI: 10.1006/niox.1999.0226. View

15.

Dawson-Hughes B, Looker A, Tosteson A, Johansson H, Kanis J, Melton 3rd L . The potential impact of new National Osteoporosis Foundation guidance on treatment patterns. Osteoporos Int. 2009; 21(1):41-52. DOI: 10.1007/s00198-009-1034-7. View

16.

Gomez D, Twahirwa M, Schlesinger L, Restrepo B . Reduced Mycobacterium tuberculosis association with monocytes from diabetes patients that have poor glucose control. Tuberculosis (Edinb). 2012; 93(2):192-7. PMC: 3580120. DOI: 10.1016/j.tube.2012.10.003. View

17.

Xu H, Soruri A, Gieseler R, Peters J . 1,25-Dihydroxyvitamin D3 exerts opposing effects to IL-4 on MHC class-II antigen expression, accessory activity, and phagocytosis of human monocytes. Scand J Immunol. 1993; 38(6):535-40. DOI: 10.1111/j.1365-3083.1993.tb03237.x. View

18.

Chang J, Kuo M, Kuo H, Hwang S, Tsai J, Chen H . 1-alpha,25-Dihydroxyvitamin D3 regulates inducible nitric oxide synthase messenger RNA expression and nitric oxide release in macrophage-like RAW 264.7 cells. J Lab Clin Med. 2004; 143(1):14-22. DOI: 10.1016/j.lab.2003.08.002. View

19.

Rockett K, Brookes R, Udalova I, Vidal V, Hill A, Kwiatkowski D . 1,25-Dihydroxyvitamin D3 induces nitric oxide synthase and suppresses growth of Mycobacterium tuberculosis in a human macrophage-like cell line. Infect Immun. 1998; 66(11):5314-21. PMC: 108664. DOI: 10.1128/IAI.66.11.5314-5321.1998. View

20.

Chandra G, Selvaraj P, Jawahar M, Banurekha V, Narayanan P . Effect of vitamin D3 on phagocytic potential of macrophages with live Mycobacterium tuberculosis and lymphoproliferative response in pulmonary tuberculosis. J Clin Immunol. 2004; 24(3):249-57. DOI: 10.1023/B:JOCI.0000025446.44146.52. View