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Stendahl, Olle
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Abate, E., Belayneh, M., Idh, J., Diro, E., Elias, D., Britton, S., . . . Schön, T. (2015). Asymptomatic Helminth Infection in Active Tuberculosis Is Associated with Increased Regulatory and Th-2 Responses and a Lower Sputum Smear Positivity. PLoS Neglected Tropical Diseases, 9(8), Article ID e0003994.
Open this publication in new window or tab >>Asymptomatic Helminth Infection in Active Tuberculosis Is Associated with Increased Regulatory and Th-2 Responses and a Lower Sputum Smear Positivity
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2015 (English)In: PLoS Neglected Tropical Diseases, ISSN 1935-2727, E-ISSN 1935-2735, Vol. 9, no 8, article id e0003994Article in journal (Refereed) Published
Abstract [en]

Background The impact of intestinal helminth infection on the clinical presentation and immune response during active tuberculosis (TB) infection is not well characterized. Our aim was to investigate whether asymptomatic intestinal helminth infection alters the clinical signs and symptoms as well as the cell mediated immune responses in patients with active TB.

Methodology Consecutive, newly diagnosed TB patients and healthy community controls (CCs) were recruited in North-west Ethiopia. TB-score, body mass index and stool samples were analyzed. Cells from HIV-negative TB patients (HIV-/TB) and from CCs were analyzed for regulatory T-cells (Tregs) and cytokine responses using flow cytometry and ELISPOT, respectively.

Results A significantly higher ratio of helminth co-infection was observed in TB patients without HIV (Helm+/HIV-/TB) compared to HIV negative CCs, (40% (121/306) versus 28% (85/306), p = 0.003). Helm+/HIV-/TB patients showed significantly increased IL-5 secreting cells compared to Helm-/HIV-/TB (37 SFU (IQR:13-103) versus 2 SFU (1-50); p = 0.02, n = 30). Likewise, levels of absolute Tregs (9.4 (3.2-16.7) cells/mu l versus 2.4 (1.1-4.0) cells/mu l; p = 0.041) and IL-10 secreting cells (65 SFU (7-196) versus 1 SFU (0-31); p = 0.014) were significantly higher in Helm+/HIV-/TB patients compared to Helm-/HIV-/TB patients. In a multivariate analysis, a lower rate of sputum smear positivity for acid fast bacilli, lower body temperature, and eosinophilia were independently associated with helminth infection in TB patients.

Conclusions Asymptomatic helminth infection is associated with increased regulatory T-cell and Th2-type responses and a lower rate of sputum smear positivity. Further studies are warranted to investigate the clinical and immunological impact of helminth infection in TB patients.

Place, publisher, year, edition, pages
PUBLIC LIBRARY SCIENCE, 2015
National Category
Microbiology in the medical area
Identifiers
urn:nbn:se:liu:diva-121763 (URN)10.1371/journal.pntd.0003994 (DOI)000360708200058 ()26248316 (PubMedID)
Note

Funding Agencies|SAREC/SIDA; EU/EDCTP [JP 10800.006]; Swedish Research Council; Swedish Heart and Lung Foundation (Oscar II Jubilee Foundation); Wallenberg Foundation; Armauer Hansen Research Institute

Available from: 2015-10-06 Created: 2015-10-05 Last updated: 2018-01-11
Abate, E., Elias, D., Getachew, A., Alemu, S., Diro, E., Britton, S., . . . Schön, T. (2015). Effects of albendazole on the clinical outcome and immunological responses in helminth co-infected tuberculosis patients: a double blind randomised clinical trial. International Journal of Parasitology, 45(2-3), 133-140
Open this publication in new window or tab >>Effects of albendazole on the clinical outcome and immunological responses in helminth co-infected tuberculosis patients: a double blind randomised clinical trial
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2015 (English)In: International Journal of Parasitology, ISSN 0020-7519, E-ISSN 1879-0135, Vol. 45, no 2-3, p. 133-140Article in journal (Refereed) Published
Abstract [en]

Despite several review papers and experimental studies concerning the impact of chronic helminth infection on tuberculosis in recent years, there is a scarcity of data from clinical field studies in highly endemic areas for these diseases. We believe this is the first randomised clinical trial investigating the impact of albendazole treatment on the clinical and immunological outcomes of helminth co-infected tuberculosis patients. A randomised, double-blind, placebo-controlled trial of albendazole (400 mg per day for 3 days) in helminth-positive tuberculosis patients was conducted in Gondar, Ethiopia. The primary outcome was clinical improvement (Delta TB score) after 2 months. Among secondary outcomes were changes in the levels of eosinophils, CD4+ T cells, regulatory T cells, IFN-gamma, IL-5 and IL-10 after 3 months. A total of 140 helminth co-infected tuberculosis patients were included with an HIV co-infection rate of 22.8%. There was no significant effect on the primary outcome (Delta TB score: 5.6 +/- 2.9 for albendazole versus 5.9 +/- 2.5 for placebo, P = 0.59). The albendazole-treated group showed a decline in eosinophil cells (P = 0.001) and IL-10 (P = 0.017) after 3 months. In an exploratory analysis after 12 weeks, the albendazole treated group showed a trend towards weight gain compared with the placebo group (11.2 +/- 8.5 kg versus 8.2 +/- 8.7 kg, P = 0.08)). The reductions in eosinophil counts and IL-10 show that asymptomatic helminth infection significantly affects host immunity during tuberculosis and can be effectively reversed by albendazole treatment. The clinical effects of helminth infection on chronic infectious diseases such as tuberculosis merit further characterisation. (C) 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

Place, publisher, year, edition, pages
Elsevier, 2015
Keywords
Helminth; Tuberculosis; Albendazole; Deworming; HIV; Ethiopia
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-116974 (URN)10.1016/j.ijpara.2014.09.006 (DOI)000350936200006 ()25486494 (PubMedID)
Note

Funding Agencies|Swedish Research Council; Swedish Heart and Lung Foundation; King Oscar II Jubilee Foundation; SIDA/SAREC; European and Developing Countries Clinical Trials Partnership (EDCTP) [JP]; Groschinsky Memorial Foundation; Marianne and Marcus Wallenberg foundation

Available from: 2015-04-10 Created: 2015-04-10 Last updated: 2017-12-04
Andersson, H., Eklund, D., Ngoh, E., Persson, A., Andersson, B., Svensson, K., . . . Stendahl, O. (2014). Apoptotic neutrophils augment the inflammatory response to Mycobacterium tuberculosis infection in human macrophages. PLoS ONE, 9(7), e101514
Open this publication in new window or tab >>Apoptotic neutrophils augment the inflammatory response to Mycobacterium tuberculosis infection in human macrophages
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2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 7, p. e101514-Article in journal (Refereed) Published
Abstract [en]

Macrophages in the lung are the primary cells being infected by Mycobacterium tuberculosis (Mtb) during tuberculosis. Innate immune cells such as macrophages and neutrophils are first recruited to the site of infection, and mount the early immune protection against this intracellular pathogen. Neutrophils are short-lived cells and removal of apoptotic cells by resident macrophages is a key event in the resolution of inflammation and tissue repair. Such anti-inflammatory activity is not compatible with effective immunity to intracellular pathogens. We therefore investigated how uptake of apoptotic neutrophils by Mtb-activated human monocyte-derived macrophages modulates their function. We show that Mtb infection exerts a potent pro-inflammatory activation of human macrophages with enhanced gene activation and release of several cytokines (TNF, IL-1ß, IL-6, IL-18 and IL-10). This response was augmented by apoptotic neutrophils. Macrophages containing both Mtb and apoptotic cells showed a stronger cytokine expression than non-infected cells. The enhanced macrophage response is linked to apoptotic neutrophil-driven activation of the NLRP3 inflammasome and subsequent IL-1β signalling. We also demonstrate that apoptotic neutrophils not only modulate the inflammatory response, but also enhance the capacity of infected macrophages to control intracellular growth of virulent Mtb. Taken together, these results suggest a novel role for apoptotic neutrophils in the modulation of the macrophage-dependent inflammatory response, which can contribute to the early control of Mtb infection.

Place, publisher, year, edition, pages
PLoS, 2014
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-100888 (URN)10.1371/journal.pone.0101514 (DOI)000338637300054 ()
Available from: 2013-11-14 Created: 2013-11-14 Last updated: 2017-12-06Bibliographically approved
Eklund, D., Welin, A., Andersson, H., Verma, D., Söderkvist, P., Stendahl, O., . . . Lerm, M. (2014). Human gene variants linked to enhanced NLRP3 activity limit intramacrophage growth of Mycobacterium tuberculosis. The Journal of infectious diseases, 209(5), 749-753
Open this publication in new window or tab >>Human gene variants linked to enhanced NLRP3 activity limit intramacrophage growth of Mycobacterium tuberculosis
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2014 (English)In: The Journal of infectious diseases, ISSN 1537-6613, Vol. 209, no 5, p. 749-753Article in journal (Refereed) Published
Abstract [en]

Activation of the NLRP3 inflammasome and subsequent generation of IL-1β is initiated in macrophages upon recognition of several stimuli. In the present work, we show that gain-of-function gene variants of inflammasome components known to predispose individuals to inflammatory disorders have a host-protective role during infection with Mycobacterium tuberculosis. By isolation of macrophages from patients and healthy blood donors with genetic variants in NLRP3 and CARD8 and subsequently infecting the cells by virulent M. tuberculosis, we show that these gene variants, combined, are associated with increased control of bacterial growth in human macrophages.

Place, publisher, year, edition, pages
University of Chicago Press / Oxford University Press (OUP), 2014
National Category
Clinical Medicine
Identifiers
urn:nbn:se:liu:diva-100889 (URN)10.1093/infdis/jit572 (DOI)000331873700016 ()24158955 (PubMedID)
Available from: 2013-11-14 Created: 2013-11-14 Last updated: 2015-04-10Bibliographically approved
Persson, H. L., Eklund, D., Welin, A., Paues, J., Idh, J., Fransson, S.-G., . . . Schön, T. (2013). Alveolar macrophages from patients with tuberculosis exhibit reduced capacity of restricting growth of Mycobacterium tuberculosis: a pilot study of vitamin D stimulation in vitro. HOAJ Biology
Open this publication in new window or tab >>Alveolar macrophages from patients with tuberculosis exhibit reduced capacity of restricting growth of Mycobacterium tuberculosis: a pilot study of vitamin D stimulation in vitro
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2013 (English)In: HOAJ Biology, ISSN 2050-0874Article in journal (Refereed) Published
Abstract [en]

Background: The role of vitamin D supplementation as adjuvant treatment of tuberculosis (TB) has lately attracted increasing interest. Our aim was to investigate the capacity of alveolar macrophages (AMs) from patients with or without exposure to TB to control intracellular growth of virulent Mycobacterium tuberculosis (Mtb).

Methods: AMs were freshly harvested from the bronchoalveolar lavage fluid of 7 patients with a history of TB (4 patients with previous TB and 3 patients with current TB) and 4 non-TB subjects. The H37Rv strain, genetically modified to express Vibrio harveyi luciferase, was used to determine the growth of Mtb by luminometry in the AMs from study subjects. Cytokine levels in culture supernatants were determined using a flow cytometry-based bead array technique.

Results: AMs from patients with a TB history were less efficient in restricting Mtb growth. Stimulation with 100 nM1, 25-dihydroxyvitamin D (1,25D3) did not significantly influence the capacity of AMs from any study subjects to control the infection. Out of the cytokines evaluated (TNF-α, IL-1β, IL-10 and IL-12p40) only TNF-α demonstrated detectable levels in culture supernatants, but did not respond to stimulation with 1,25D3.

Conclusions: We conclude that AMs of TB-patients show reduced ability to control mycobacterial growth in vitro, and, that AMs in this pilot study do no respond to 1, 25D3-stimulation. The former observation supports the concept that innate immunity is crucial for the control of TB infection.

Place, publisher, year, edition, pages
United Kingdom: Herbert Publications Ltd, 2013
Keywords
Alveolar macrophages, bronchoalveolar lavage, cytokines, H37Rv, tuberculosis
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-91314 (URN)10.7243/2052-6180-1-6 (DOI)
Available from: 2013-04-22 Created: 2013-04-22 Last updated: 2018-03-26
Abate, E., Elias, D., Getachew, A., Alemu, S., Diro, E., Britton, S., . . . Schön, T. (2013). Effects of albendazole treatment on the clinical outcome and immunological responses in patients with helminth infection and pulmonary tuberculosis: a randomized clinical trial.
Open this publication in new window or tab >>Effects of albendazole treatment on the clinical outcome and immunological responses in patients with helminth infection and pulmonary tuberculosis: a randomized clinical trial
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2013 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: The impact of helminth infection on the host immune response to tuberculosis (TB) has been characterized in experimental models but less so in the clinical setting. The objective of this study was to investigate the impact of deworming on the clinical outcome and cell mediated immune response in active TB.

Methods: Newly diagnosed pulmonary TB patients in Gondar, Ethiopia were examined for helminth infection. Helminth-positive TB patients (W+/TB) were randomized to albendazole (400mg X III per os) or placebo. The primary outcome was change in TB-score after 2 months, and secondary outcomes were sputum smear conversion at the 2nd month, and changes in chest x-ray pattern, CD4+ T-cell count, eosinophil count, IgE-levels and immunological responses after 3 months. In a subset of W+/TB, W-/TB patients and healthy controls, flow cytometry and ELISPOT assays were used to characterize the regulatory T-cell population (Tregs) and the frequency of PPD- stimulated IFN-γ, IL-5 and IL-10 producing peripheral blood mononuclear cells (PBMCs).

Results: A total of 140 helminth co-infected TB patients were included with an HIV coinfection rate of 22.8 %. Following albendazole treatment of the W+/TB patients, there was a significant decrease in helminth infection compared to placebo (8% (4/49) vs. 48 % (22/46), p<0.001). No significant effect was observed for albendazole compared to placebo on the primary outcome as evaluated by the TB-score (5.6 ±2.87 vs. 5.87 ±2.54, p=0.59). Eosinophil counts decreased significantly in the albendazole group. In a subgroup analysis of helminthnegative patients following albendazole treatment versus placebo, the albendazole group showed a trend for lower levels of IL-10 producing cells at month three (p=0.08). At baseline, W+/TB patients had a significantly higher mean level of Tregs (% Tregs/CD4+) compared to W-/TB patients and helminth-positive community controls. Additionally, the frequency of IFN-γ, IL-5 and spontaneous IL-10 levels was increased in helminth-positive compared to helminth-negative TB patients.

Conclusions: No significant effects on the clinical outcome as measured with the TB-score was detected after albendazole treatment of helminth-positive TB patients compared to placebo. However, significant changes were observed in specific immunological responses such as reduced eosinophil counts and a trend towards lower levels of IL-10 producing cells. At baseline, helminth co-infected TB patients exhibited an increased Treg response as well as an increased IL-5 and spontaneous IL-10 production.

Keywords
Regulatory T-cells, helminth, tuberculosis, albendazole, deworming, Ethiopia, HIV
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-91827 (URN)
Available from: 2013-05-02 Created: 2013-05-02 Last updated: 2013-05-02Bibliographically approved
Abate, E., Idh, J., Belayneh, M., Getachew, A., Alemu, S., Diro, E., . . . Schön, T. (2013). Impact of helminth infection on the clinical presentation 1 of pulmonary tuberculosis.
Open this publication in new window or tab >>Impact of helminth infection on the clinical presentation 1 of pulmonary tuberculosis
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2013 (English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: The effects of helminth infection on chronic infectious diseases such as HIV and tuberculosis (TB) merit further characterization. Thus, we assessed the baseline clinical characteristics of helminth infection in patients with active TB in a high endemic area.

Methodology: Consecutive, newly diagnosed TB patients were recruited from three health institutions in the north Gondar administrative zone, Ethiopia. Structured questionnaires were used to collect socio-demographic and clinical characteristics. Additionally, the TB score, mid upper arm circumference, body mass index (BMI), BCG vaccination status, stool and sputum microscopy as well as HIV serology and CD4+T cells counts were evaluated.

Results: A total of 377 pulmonary TB patients were included in the study. The helminth co infection rate was 33% (123/377) and the most prevalent parasite was Ascaris lumbricoides (53%, 65/123). The HIV co-infection rate was 29% (110/377). Seventy percent (77/110) of the HIV co-infected patients were on anti- retroviral therapy at the time of TB diagnosis. Helminth infection was more prevalent in HIV-negative TB patients compared to HIV-positive TB patients (p=0.025). Smoking and walking bare foot were independently associated to helminth infection in TB patients after adjusting for the influence of HIV. Other than increased eosinophilia, no other significant differences were observed between helminth positive and helminth negative TB patients in the clinical presentation including the TB score, CD4+T-cells, BMI or bacterial load.

Conclusion: The clinical presentation of active pulmonary tuberculosis was not affected by helminth infection. Helminth infection was less frequent among HIV-positive TB patients and this finding merits further investigation.

Keywords
Tuberculosis, HIV, helminth, TB score, CD4, Ethiopia
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-91825 (URN)
Available from: 2013-05-02 Created: 2013-05-02 Last updated: 2013-05-02Bibliographically approved
Braian, C., Hogea, V. & Stendahl, O. (2013). Mycobacterium tuberculosis-Induced Neutrophil Extracellular Traps Activate Human Macrophages. Journal of Innate Immunity, 5(6), 591-602
Open this publication in new window or tab >>Mycobacterium tuberculosis-Induced Neutrophil Extracellular Traps Activate Human Macrophages
2013 (English)In: Journal of Innate Immunity, ISSN 1662-811X, E-ISSN 1662-8128, Vol. 5, no 6, p. 591-602Article in journal (Refereed) Published
Abstract [en]

Neutrophils activated by Mycobacterium tuberculosis (Mtb) form neutrophil extracellular traps (NETs), containing DNA and several biologically active cytosolic and granular proteins. These NETs may assist in the innate immune defense against different pathogens. We investigated whether the NET-forming neutrophils mediate an activating signal to macrophages during the early multicellular inflammatory reaction and granuloma formation. Mtb-induced NETs were found to be reactive oxygen species dependent and phagocytosis dependent. A neutrophil elastase inhibitor also delayed NET formation. However, NET formation occurred independently of Mtb-induced apoptosis. We observed close interactions between macrophages and Mtb-activated neutrophils, where macrophages bound and phagocytosed NETs. Significant secretion of the cytokines interleukin (IL)-6, tumor necrosis factor-alpha, IL-1 beta and IL-10 were detected from macrophages cocultured with NETs from Mtb-activated but not phorbol myristate acetate-activated neutrophils. NETs binding heat shock protein 72 (Hsp72) or recombinant Hsp72 were able to trigger cytokine release from macrophages. Only Mtb-induced NETs contained Hsp72, suggesting that these NETs can transfer this danger signal to adjacent macrophages. We propose that Hsp72 sequestered in NETs plays an important role in the interaction between neutrophils and macrophages during the early innate immune phase of an Mtb infection. The immunomodulatory role of NETs and proteins derived from them may influence not only chronic inflammation during tuberculosis but also immune regulation and autoimmunity.

Place, publisher, year, edition, pages
Karger, 2013
Keywords
Mycobacterium tuberculosis, Neutrophil extracellular traps, Heat shock protein 72, Neutrophil, Macrophage, Innate immunity
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-102507 (URN)10.1159/000348676 (DOI)000327052400006 ()
Note

Funding Agencies|Swedish Research Council||Ragnar Soderbergs Foundation||Sida||Swedish Heart and Lung Foundation||

Available from: 2013-12-12 Created: 2013-12-12 Last updated: 2019-02-11
Schon, T., Lerm, M. & Stendahl, O. (2013). Shortening the short-course therapy-insights into host immunity may contribute to new treatment strategies for tuberculosis. Journal of Internal Medicine, 273(4), 368-382
Open this publication in new window or tab >>Shortening the short-course therapy-insights into host immunity may contribute to new treatment strategies for tuberculosis
2013 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 273, no 4, p. 368-382Article, review/survey (Refereed) Published
Abstract [en]

Schon T, Lerm M, Stendahl O (Kalmar County Hospital, Kalmar; and Linkoping University, Linkoping; Sweden). Shortening the short-course therapy: insights into host immunity may contribute to newtreatment strategies for tuberculosis (Review). J Intern Med 2013; 273: 368-382. Achieving global control of tuberculosis (TB) is a great challenge considering the current increase in multidrug resistance and mortality rate. Considerable efforts are therefore being made to develop new effective vaccines, more effective and rapid diagnostic tools as well as new drugs. Shortening the duration of TB treatment with revised regimens and modes of delivery of existing drugs, as well as development of new antimicrobial agents and optimization of the host response with adjuvant immunotherapy could have a profound impact on TB cure rates. Recent data show that chronic worm infection and deficiencies in micronutrients such as vitamin D and arginine are potential areas of intervention to optimize host immunity. Nutritional supplementation to enhance nitric oxide production and vitamin D-mediated effector functions as well as the treatment of worm infection to reduce immunosuppressive effects of regulatory T (Treg) lymphocytes may be more suitable and accessible strategies for highly endemic areas than adjuvant cytokine therapy. In this review, we focus mainly on immune control of human TB, and discuss how current treatment strategies, including immunotherapy and nutritional supplementation, could be optimized to enhance the host response leading to more effective treatment.

Place, publisher, year, edition, pages
Wiley-Blackwell, 2013
Keywords
macrophage, nitric oxide, nutrition, tuberculosis, vitamin D
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-91338 (URN)10.1111/joim.12031 (DOI)000316631400007 ()
Note

Funding Agencies|Swedish Research Council||Heart-Lung Foundation||Swedish International Development Agency||European developing countries clinical trial partnership (ED-CTP)||Swedish Society of Medicine||Medical Research Council of Southeast Sweden||M&M Wallenberg Foundation||R Soderberg Foundation||B&M Gates Foundation||

Available from: 2013-04-22 Created: 2013-04-22 Last updated: 2017-12-06
Eklund, D., Persson, H. L., Larsson, M. C., Welin, A., Idh, J., Paues, J., . . . Lerm, M. (2013). Vitamin D enhances IL-1β secretion and restricts growth of Mycobacterium tuberculosis in macrophages from TB patients. International Journal of Mycobacteriology, 2(1), 18-25
Open this publication in new window or tab >>Vitamin D enhances IL-1β secretion and restricts growth of Mycobacterium tuberculosis in macrophages from TB patients
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2013 (English)In: International Journal of Mycobacteriology, ISSN 2212-5531, Vol. 2, no 1, p. 18-25Article in journal (Refereed) Published
Abstract [en]

The emergence of multidrug-resistant strains of Mycobacterium tuberculosis (MTB), the bacterium responsible for tuberculosis (TB), has rekindled the interest in the role of nutritional supplementation of micronutrients, such as vitamin D, as adjuvant treatment. Here, the growth of virulent MTB in macrophages obtained from the peripheral blood of patients with and without TB was studied. The H37Rv strain genetically modified to express Vibrio harveyi luciferase was used to determine the growth of MTB by luminometry in the human monocyte-derived macrophages (hMDMs) from study subjects. Determination of cytokine levels in culture supernatants was performed using a flow cytometry-based bead array technique. No differences in intracellular growth of MTB were observed between the different study groups. However, stimulation with 100 nM 1,25-dihydroxyvitamin D significantly enhanced the capacity of hMDMs isolated from TB patients to control the infection. This effect was not observed in hMDMs from the other groups. The interleukin (IL)-1β and IL-10 release by hMDMs was clearly increased upon stimulation with 1,25-dihydroxyvitamin D. Furthermore, the 1,25-dihydroxyvitamin D stimulation also led to elevated levels of TNF-α (tumor necrosis factor-alpha) and IL-12p40. It was concluded that vitamin D triggers an inflammatory response in human macrophages with enhanced secretion of cytokines, as well as enhancing the capacity of hMDMs from patients with active TB to restrict mycobacterial growth.

Place, publisher, year, edition, pages
Netherlands: Elsevier, 2013
Keywords
Vitamin D, Human macrophages, Intracellular growth, TB patients, IL-1β
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-90356 (URN)10.1016/j.ijmyco.2012.11.001 (DOI)
Available from: 2013-03-25 Created: 2013-03-25 Last updated: 2018-03-26
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