Th3 Immune responses in the progression of leprosy via molecular cross-talks of TGF-β, CTLA-4 and Cbl-b

Abstract Leprosy is a chronic human disease; primarily affecting skin, peripheral nerves, eyes, testis etc. Comprehensive-expressional-profiling of Th1–Th2–Th3 associated markers (84 genes) using qRT-PCR array, negated the previously prevailing notion, Th2 bias towards multibacillary stage of lepros...

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Published in:Clinical immunology (Orlando, Fla.) Fla.), 2011-11, Vol.141 (2), p.133-142
Main Authors: Kumar, Sudhir, Naqvi, Raza A, Khanna, Neena, Pathak, Pankaj, Rao, D.N
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - biosynthesis
Adaptor Proteins, Signal Transducing - genetics
Adaptor Proteins, Signal Transducing - immunology
Allergy and Immunology
Amino Acid Sequence
Antibodies, Monoclonal - pharmacology
Antigens, Bacterial - immunology
Bacterial diseases
Biological and medical sciences
Cell Lineage
Cell Wall - immunology
Cells, Cultured
CTLA-4 Antigen - antagonists & inhibitors
CTLA-4 Antigen - genetics
CTLA-4 Antigen - immunology
Cytokines - secretion
Disease Progression
Fundamental and applied biological sciences. Psychology
Fundamental immunology
Gene Expression Profiling
Gene Expression Regulation
Human bacterial diseases
Humans
Immune Tolerance
Immunity, Cellular
Infectious diseases
Leprosy
Leprosy, Multibacillary - genetics
Leprosy, Multibacillary - immunology
Leprosy, Paucibacillary - genetics
Leprosy, Paucibacillary - immunology
Medical sciences
MLCwA
Molecular Sequence Data
Mycobacterium leprae
Mycobacterium leprae - immunology
Proto-Oncogene Proteins c-cbl - biosynthesis
Proto-Oncogene Proteins c-cbl - genetics
Proto-Oncogene Proteins c-cbl - immunology
RNA, Small Interfering - pharmacology
T-Lymphocytes, Regulatory - immunology
TGF-β
Th1 Cells - immunology
Th2 Cells - immunology
Th3
Transforming Growth Factor beta - antagonists & inhibitors
Transforming Growth Factor beta - biosynthesis
Transforming Growth Factor beta - genetics
Transforming Growth Factor beta - immunology
Tropical bacterial diseases
Tuberculosis and atypical mycobacterial infections
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Summary:Abstract Leprosy is a chronic human disease; primarily affecting skin, peripheral nerves, eyes, testis etc. Comprehensive-expressional-profiling of Th1–Th2–Th3 associated markers (84 genes) using qRT-PCR array, negated the previously prevailing notion, Th2 bias towards multibacillary stage of leprosy. High production TGF-β further supported the dearth of any immune response(s) in leprosy progression. Over expression of Cbl-b, could emerge as plausible reason for contributing T cell hyporesponsiveness, possibly by degradation of T cells signaling molecules. Anti-TGF-β treatments further confirm the TGF-β-dependent-Cbl-b overexpression in multibacillary patients. Diminished Cbl-b expression in CTLA-4 knockout studies using siRNA, provided other evidence towards T cell hyporesponsiveness. Further, high T cell proliferation and IL-2 production in PBMC cultures treated with anti-TGF-β and siRNA offers here a strategy to revert T cell hyporesponsiveness by downregulating Cbl-b expression in leprosy. Thus, this study negates Th2 bias and substantiates molecular cross-talk amongst TGF-β-CTLA-4-Cbl-b eventually leads to M. leprae persistence.
ISSN:1521-6616
1521-7035
DOI:10.1016/j.clim.2011.06.007