Medical Hypotheses xxx (2015) xxx–xxx
Contents lists available at ScienceDirect
Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy
Correspondence Preventing Mycobacterium tuberculosis infection by enhancement of innate immunity
To the editor, In a recent article the authors proposed a combination of Vitamin A and Vitamin D as a way to prevent and treat tuberculosis [1]. The authors claim that a major limitation of the BCG vaccination is its failure to prevent latent tuberculosis. This is not entirely accurate. We recently demonstrated that across different geographical settings BCG can prevent Mycobacterium tuberculosis infection with a vaccine efficacy of up to 27% [2]. The reduced probability of infection in BCG immunised exposed children was compatible with an enhancement of innate immunity of macrophages by BCG eliminating infection [3]. The enhancement of antimycobacterial activity of macrophages by Vitamin A and D described could equally be used to prevent the establishment of the infection event at the entry point of M. tuberculosis in the lung. Treatment of active tuberculosis by Vitamins alone is unlikely to be effective in eradication of M. tuberculosis from the body once infection is established for example in caseating lesions with no viable macrophages in the vicinity. Future studies need to include prospective randomized controlled trials of prevention of M. tuberculosis infection comparing infection rates in people with and without Vitamin A and/or Vitamin D supplementation. Animal studies need to explore anti-mycobacterial innate immunity in macrophages like pattern recognition receptor signalling including Toll Like Receptor 2 (TLR-2) signalling by action of muramyl dipeptide derivatives with a single octanoyl or stearoyl fatty acid chain, Nucleotide oligomerisation domain (NOD) 1 by H-Ala-D-c-Glu-diaminopimelic acid and NOD 2 signalling by use of muramyl
http://dx.doi.org/10.1016/j.mehy.2015.06.030 0306-9877/Ó 2015 Published by Elsevier Ltd.
dipeptide, which is a stimulator of NOD expression. Simultaneous stimulation of TLR 2 and NOD 2 has hereby been shown to be associated with a synergistic effect on antimycobacterial cytokine production [4]. Conflict of interest None. References [1] Syal K, Chakraborty S, Bhattacharyya R, Banerjee D. Combined inhalation and oral supplementation of Vitamin A and Vitamin D: a possible prevention and therapy for tuberculosis. Med Hypotheses 2015;84:199–203. [2] Roy A, Eisenhut M, Harris RJ, et al. The protective effect of BCG vaccination against mycobacterium tuberculosis Infection in children: a systematic review and meta-analysis. BMJ 2014;349:g4643. http://dx.doi.org/10.1136/bmj.g4643. [3] Eisenhut M. Reduction of Mycobacterium tuberculosis infection in Bacillus Calmette Guerin immunized people is due to training of innate immunity. Med Hypotheses 2015;84:189–93. [4] Ferwerda G, Girardin SE, Kullberg BJ, et al. NOD2 and toll-like receptors are nonredundant recognition systems of Mycobacterium tuberculosis. PLoS Pathog 2005;1:279–85.
Michael Eisenhut Luton & Dunstable University Hospital NHS Foundation Trust, Lewsey Road, Luton LU4ODZ, United Kingdom Tel.: +44 0845 1270127. E-mail address: [email protected] Available online xxxx
Contents lists available at ScienceDirect
Medical Hypotheses journal homepage: www.elsevier.com/locate/mehy
Correspondence Preventing Mycobacterium tuberculosis infection by enhancement of innate immunity
To the editor, In a recent article the authors proposed a combination of Vitamin A and Vitamin D as a way to prevent and treat tuberculosis [1]. The authors claim that a major limitation of the BCG vaccination is its failure to prevent latent tuberculosis. This is not entirely accurate. We recently demonstrated that across different geographical settings BCG can prevent Mycobacterium tuberculosis infection with a vaccine efficacy of up to 27% [2]. The reduced probability of infection in BCG immunised exposed children was compatible with an enhancement of innate immunity of macrophages by BCG eliminating infection [3]. The enhancement of antimycobacterial activity of macrophages by Vitamin A and D described could equally be used to prevent the establishment of the infection event at the entry point of M. tuberculosis in the lung. Treatment of active tuberculosis by Vitamins alone is unlikely to be effective in eradication of M. tuberculosis from the body once infection is established for example in caseating lesions with no viable macrophages in the vicinity. Future studies need to include prospective randomized controlled trials of prevention of M. tuberculosis infection comparing infection rates in people with and without Vitamin A and/or Vitamin D supplementation. Animal studies need to explore anti-mycobacterial innate immunity in macrophages like pattern recognition receptor signalling including Toll Like Receptor 2 (TLR-2) signalling by action of muramyl dipeptide derivatives with a single octanoyl or stearoyl fatty acid chain, Nucleotide oligomerisation domain (NOD) 1 by H-Ala-D-c-Glu-diaminopimelic acid and NOD 2 signalling by use of muramyl
http://dx.doi.org/10.1016/j.mehy.2015.06.030 0306-9877/Ó 2015 Published by Elsevier Ltd.
dipeptide, which is a stimulator of NOD expression. Simultaneous stimulation of TLR 2 and NOD 2 has hereby been shown to be associated with a synergistic effect on antimycobacterial cytokine production [4]. Conflict of interest None. References [1] Syal K, Chakraborty S, Bhattacharyya R, Banerjee D. Combined inhalation and oral supplementation of Vitamin A and Vitamin D: a possible prevention and therapy for tuberculosis. Med Hypotheses 2015;84:199–203. [2] Roy A, Eisenhut M, Harris RJ, et al. The protective effect of BCG vaccination against mycobacterium tuberculosis Infection in children: a systematic review and meta-analysis. BMJ 2014;349:g4643. http://dx.doi.org/10.1136/bmj.g4643. [3] Eisenhut M. Reduction of Mycobacterium tuberculosis infection in Bacillus Calmette Guerin immunized people is due to training of innate immunity. Med Hypotheses 2015;84:189–93. [4] Ferwerda G, Girardin SE, Kullberg BJ, et al. NOD2 and toll-like receptors are nonredundant recognition systems of Mycobacterium tuberculosis. PLoS Pathog 2005;1:279–85.
Michael Eisenhut Luton & Dunstable University Hospital NHS Foundation Trust, Lewsey Road, Luton LU4ODZ, United Kingdom Tel.: +44 0845 1270127. E-mail address: [email protected] Available online xxxx
