Abstract
BackgroundLeprosy is an ideal human disease to study T cell regulation as patients show correlation between cytokine skewed Th1-Th2 responses and clinical forms of the disease. The Role of transcription factors on the modulation of Th1 and Th2 responses by M. leprae antigens has not been adequately studied. In the present study, we studied the effect of M. leprae antigens on transcription factors STAT-4, STAT-6 and CREB and their correlation with Th1/Th2 cell mediated immune responses in leprosy.MethodsLeprosy patients of both categories of tuberculoid leprosy (BT/TT) and lepromatous leprosy (BL/LL) were selected from the OPD of NJ1L & OMD, (ICMR), Agra and healthy individuals (H) were chosen from the staff and students working in the institute. Peripheral blood mononuclear cells (PBMCs) of the study subjects were stimulated with M. leprae antigens (WCL, MLSA, and PGL-1). Sandwich ELISA was done in the culture supernatants of healthy and leprosy patients to detect IL-4, IL-10 and IFN-γ. Further, expression of IFN-γ and IL-4 and activation of STAT4, STAT6 and CREB transcription factors in CD4+ T cell with or without stimulation of M. leprae antigens was investigated by flow cytometry.ResultsLepromatous leprosy patients showed significantly lower IFN-γ and higher IL-4 levels in culture supernatant and significantly low expression of IFN-γ and higher expression of IL-4 by CD4+ T cells than healthy individuals with or without antigenic stimulation. Antigenic stimulation significantly increased IL-10 in BL/LL patients but not in BT/TT patients or healthy individuals. PGL-1 stimulation led to significantly higher activation of STAT-6 in BT/TT and BL/LL patients in comparison to healthy individuals. All the three antigens led to activation of CREB in healthy and BT/TT patients but not in BL/LL patients.ConclusionOur findings show that M. leprae antigens differentially modulate activation of T cell transcription factors STAT-4/STAT-6 and CREB. These transcription factors are well known to regulate Th1 and Th2 mediated immune response which in turn could play vital role in the clinical manifestations of leprosy. These observations may help to determine how these T cell transcription factors affect the development of immune dysfunction and whether these new pathways have a role in immunomodulation in intracellular diseases like leprosy and TB.
Highlights
Leprosy is an ideal human disease to study T cell regulation as patients show correlation between cytokine skewed Th1-Th2 responses and clinical forms of the disease
M. leprae mediated secretion of Th1/Th2 cytokines in the culture supernatant of Peripheral blood mononuclear cells (PBMC) of leprosy patients and healthy individuals PBMCs of leprosy patients (BT/Tuberculoid type (TT), Borderline lepromatous leprosy (BL)/Lepromatous lepromatous leprosy (LL)) and healthy individuals (H) were stimulated with M. leprae antigens (MLSA, Whole cell lysate (WCL) and Phenolic glycolipid (PGL)-1) and culture supernatants were collected after 48 h and 5 days
IFN-γ level was higher in response to Mycobacterium leprae soluble antigen (MLSA), WCL and Phenolic glycolipid-1 (PGL-1) in culture supernatant of healthy individuals as compared to lepromatous patients and tuberculoid patients
Summary
Leprosy is an ideal human disease to study T cell regulation as patients show correlation between cytokine skewed Th1-Th2 responses and clinical forms of the disease. The Role of transcription factors on the modulation of Th1 and Th2 responses by M. leprae antigens has not been adequately studied. We studied the effect of M. leprae antigens on transcription factors STAT-4, STAT-6 and CREB and their correlation with Th1/Th2 cell mediated immune responses in leprosy. Patients with strong cell mediated responses are able to restrict the infection and are grouped into Tuberculoid type (TT) whereas, patients with low cell mediated immunity and high antibody response harbor numerous organisms and are categorized as Lepromatous type (LL). Leprosy has been an extensively studied human bacterial infection in terms of Th1/ Th2 immune responses. Th1 type of immune response is characteristic of the tuberculoid form of leprosy; Th2 type immune response is dominant in the lepromatous form of leprosy
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