Immunological Cytokine Correlates of Protective Immunity and Pathogenesis in Leprosy

Abstract

The in vitro production of interferon (IFN)-g, interleukin (IL)-5, tumour necrosis factor (TNF)-a and IL-10 by blood mononuclear cells in response to whole Mycobacterium leprae and polyclonal stimulii of 23 individuals, representing a variety of conditions in relation to exposure/susceptibility to M. leprae, was assayed. In most cases, healthy household contacts of newly diagnosed multibacillary leprosy patients, designated exposed household contacts (EC), showed low-to-undetectable in vitro IFN-g production in addition to substantial TNF-a production in response to M. leprae. In contrast, peripheral blood mononuclear cells from previously exposed contacts (R) regarded as resistant-to-leprosy released low-to-moderate levels of IFN-g together with a mixed cytokine pro®le resembling a T helper (Th)0-type response. TNF-a/IL-10 ratios in response to M. leprae and Concanavalin A were signi®cantly higher in EC than in R contacts suggesting a role for the TNF-a/IL-10 ratio in restraining mycobacteria proliferation and spreading early in infection. The cytokine pro®les of leprosy patients were taken as reference points. Post-treatment lepromatous leprosy patients secreted relatively high levels of IL-10 in response to M. leprae, whereas one self-cured tuberculoid leprosy patient produced simultaneously high levels of IFN-g and TNF-a. In addition, the quantitative changes in the cytokines released by peripheral blood mononuclear cells in EC contacts after Bacille Calmette-Gue Ârin (BCG) vaccination were investigated. Vaccination induced ampli®cation of IFN-g production with a concomitant decrease in TNF-a/IL-10 ratios that resembled the cytokine pattern observed in R contacts. IFN-g production was observed in response to both a cross-reactive antigen (Ag 85) and a M. lepraespeci®c protein (MMP-I), which attests to a BCG nonspeci®c stimulation of the immune system, thereby casting these antigens as likely candidates for inclusion in a subunit vaccine against leprosy. Finally, a model for protective´pathologic response to mycobacteria is presented.

Interleukin-10 promoter single-nucleotide polymorphisms as markers for disease susceptibility and disease severity in leprosy

“…A higher tumor necrosis factor-a (TNF-a)/IL-10 ratio was correlated with a better prognosis in terms of clinical outcome of leprosy household contacts. 9 Besides, it has been suggested that IL-10 is enhanced in the MB form of the disease. 10 The IL-10 gene is located on chromosome 1q32 and microsatellites and single nucleotide polymorphisms (SNPs) are arranged to form haplotypes that are associated with levels of IL-10 production.…”

Mycobacterium bovis BCG but not Mycobacterium leprae induces TNF-alpha secretion in human monocytic THP-1 cells

“…As a first approach, we compared the level of TNF-α secretion induced in these cells after phagocytosis of Mycobacterium leprae, the causative agent of leprosy, and M. bovis BCG, an attenuated strain used as a vaccine against leprosy and tuberculosis. Blood mononuclear cells of both normal individuals or leprosy patients secrete TNF-α in response to M. leprae and BCG (Santos et al 1993, Suzuki et al 1993, Lima et al 2000. Besides its role in the differentiation of Th1 cells, TNF-α is involved in the formation of granulomas that play an essential role in preventing the extension and dissemination of mycobacterial infections (Kindler et al 1989).…”

The Effect of Black Cumin Supplementation on the Level of Interferon-γ in Multibacillary Leprosy Patient under MDT-WHO Therapy

“…Multibacillary leprosy is characterized by high bacillary load and many skin lesions. Therefore, the untreated multibacillary patients are the main source of leprosy transmission [7][8][9][10][11]. Th2 cytokine levels such as IL-4, IL-5, and IL-10 that are characteristic of lepromatous or multibacillary patients, are elevated in those patients.…”

“…Th2 cytokine levels such as IL-4, IL-5, and IL-10 that are characteristic of lepromatous or multibacillary patients, are elevated in those patients. While the level of Th1 cytokines is low, including IFNγ [8,9,12,13]. Interferon-γ is a major macrophage-activating cytokine and has a role in natural defense and cellular immunity against intracellular microbes such as M. leprae.…”