Molecular mimicry between Mycobacterium leprae proteins (50S ribosomal protein L2 and Lysyl-tRNA synthetase) and myelin basic protein: a possible mechanism of nerve damage in leprosy

Singh, Itu; Yadav, Asha Ram; Mohanty, Keshar Kunja; Katoch, Kiran; Sharma, Prashant; Mishra, B; Bisht, Deepa; Gupta, Umesh Datta; Sengupta, Utpal

doi:10.1016/j.micinf.2014.12.015

Cited by 12 publications

(18 citation statements)

References 31 publications

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“…On the contrary, in tuberculoid leprosy and during type 1 reaction (T1R), these similarities may lead to a heightened T-cell response and extensive granuloma formation while M. leprae is not observed in the host tissues ( 9 ). Our group also reported the sharing of mimicking B cell epitopes between M. leprae and the cytokeratin-10 ( 10 ) and myelin basic protein ( 11 ) of host.…”

Section: Introductionmentioning

confidence: 72%

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Autoimmunity to Tropomyosin-Specific Peptides Induced by Mycobacterium leprae in Leprosy Patients: Identification of Mimicking Proteins

et al. 2018

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BackgroundIt has been shown earlier that there is a rise in the levels of autoantibodies and T cell response to cytoskeletal proteins in leprosy. Our group recently demonstrated a rise in both T and B cell responses to keratin and myelin basic protein in all types of leprosy patients and their associations in type 1 reaction (T1R) group of leprosy.ObjectivesIn this study, we investigated the association of levels of autoantibodies and lymphoproliferation against myosin in leprosy patients across the spectrum and tried to find out the mimicking proteins or epitopes between host protein and protein/s of Mycobacterium leprae.MethodologyOne hundred and sixty-nine leprosy patients and 55 healthy controls (HC) were enrolled in the present study. Levels of anti-myosin antibodies and T-cell responses against myosin were measured by ELISA and lymphoproliferation assay, respectively. Using 2-D gel electrophoresis, western blot and MALDI-TOF/TOF antibody-reactive spots were identified. Three-dimensional structure of mimicking proteins was modeled by online server. B cell epitopes of the proteins were predicted by BCPREDS server 1.0 followed by identification of mimicking epitopes. Mice of inbred BALB/c strain were hyperimmunized with M. leprae soluble antigen (MLSA) and splenocytes and lymph node cells of these animals were adoptively transferred to naïve mice.ResultsHighest level of anti-myosin antibodies was noted in sera of T1R leprosy patients. We observed significantly higher levels of lymphoproliferative response (p < 0.05) with myosin in all types of leprosy patients compared to HC. Further, hyperimmunization of inbred BALB/c strain of female mice and rabbit with MLSA revealed that both hyperimmunized rabbit and mice evoked heightened levels of antibodies against myosin and this autoimmune response could be adoptively transferred from hyperimmunized to naïve mice. Tropomyosin was found to be mimicking with ATP-dependent Clp protease ATP-binding subunit of M. leprae. We found four mimicking epitopes between these sequences.ConclusionThese data suggest that these mimicking proteins tropomyosin and ATP-dependent Clp protease ATP-binding subunit of M. leprae or more precisely mimicking epitopes (four B cell epitopes) might be responsible for extensive tissue damage during type1 reaction in leprosy.

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Section: Introductionmentioning

confidence: 72%

“…M0273, Sigma-Aldrich Pvt. Ltd., USA) -reactive antibodies according to previously described protocol ( 11 ) with some changes. Porcine myosin (5 μg/ml) was coated into 96-well ELISA plate (flat bottom, Nunc Maxisorp, Denmark).…”

Section: Methodsmentioning

confidence: 99%

Autoimmunity to Tropomyosin-Specific Peptides Induced by Mycobacterium leprae in Leprosy Patients: Identification of Mimicking Proteins

et al. 2018

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“…Armadillo Reprograms adult Schwann cells into stem cells (Masaki et al, 2013); M. leprae antigens similar to human myelin basic protein induce autoantibodies, possibly contributing to the nerve damage associated with leprosy (Singh et al, 2015) Trachoma…”

Section: Mycobacterium Lepraementioning

confidence: 99%

The untapped cell biology of neglected tropical diseases

Sullivan

2016

MBoC

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The World Health Organization lists a constellation of 17 tropical diseases that afflict approximately one in six individuals on the planet and, until recently, few resources have been devoted to the treatment and eradication of those diseases. They are often referred to as the diseases of the “bottom billion,” because they are most prevalent among the poorest individuals in impoverished tropical nations. However, the few studies that have been performed reveal an extraordinary world of molecular and cellular adaptations that facilitate the pathogens’ survival in hosts ranging from insects to humans. A compelling case can be made that even a modest investment toward understanding the basic molecular and cell biology of these neglected pathogens has a high probability of yielding exciting new cellular mechanisms and insights into novel ways of combating these diseases.

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“…In infizierten Makrophagen bilden sich vergrößerte, blasige, mit Lipid gefüllte Phagosomen, die dann als Schaumzellen bezeichnet werden, in denen M leprae überlebt und sich vermehrt. In den Makrophagen wird das Mykobakterium über das Blut auch zum Nerven transportiert, wo nach langer Verzugszeit die Schwann-Zellen infiziert und zerstört werden [3,65]. Durch Einwandern von Entzündungszellen ver-…”

Section: Infektion Und Infektionskrankheitunclassified

“…In den Lipidorganellen kann M leprae schwer von den Antibiotika erreicht werden, was wiederum neben der sehr langsamen Replikation zu einer langen Persistenz der Mykobakterien im Organismus führt. Die Lipophilie von M leprae ist, wie oben erwähnt, ein Grund für den frühen Befall der Schwann'schen Scheide der Nervenzellen [64,65,90].…”

Section: Pathogeneseunclassified

Mycobacterium leprae – der Erreger von Lepra

2016

Bundesgesundheitsbl

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Der Arbeitskreis Blut des Bundesministeriums für Gesundheit gibt als nationales Beratungsgremium Stellungnahmen zu neuartigen Erregern ab, bewertet neue Erkenntnisse zu bekannten Erregern und erarbeitet entsprechende Empfehlungen für die Fachöffentlichkeit. Diese Serie von Stellungnahmen zu einzelnen Erregern wird als Zusammenfassung des aktuellen Wissensstandes veröffentlicht, speziell unter transfusionsmedizinisch relevanten Aspek

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Molecular mimicry between Mycobacterium leprae proteins (50S ribosomal protein L2 and Lysyl-tRNA synthetase) and myelin basic protein: a possible mechanism of nerve damage in leprosy

Cited by 12 publications

References 31 publications

Autoimmunity to Tropomyosin-Specific Peptides Induced by Mycobacterium leprae in Leprosy Patients: Identification of Mimicking Proteins

Autoimmunity to Tropomyosin-Specific Peptides Induced by Mycobacterium leprae in Leprosy Patients: Identification of Mimicking Proteins

The untapped cell biology of neglected tropical diseases

Mycobacterium leprae – der Erreger von Lepra

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