Emerging Concepts of Adaptive Immunity in Leprosy

Abstract

Leprosy is a chronic intracellular infection caused by the acid-fast bacillus, Mycobacterium leprae. The disease chiefly affects the skin, peripheral nerves, mucosa of the upper respiratory tract, and the eyes. The damage to peripheral nerves results in sensory and motor impairment with characteristic deformities and disability. Presently, the disease remains concentrated in resource-poor countries in tropical and warm temperate regions with the largest number of cases reported from India. Even though innate immunity influences the clinical manifestation of the disease, it is the components of adaptive immune system which seem to tightly correlate with the characteristic spectrum of leprosy. M. leprae-specific T cell anergy with bacillary dissemination is the defining feature of lepromatous leprosy (LL) patients in contrast to tuberculoid leprosy (TT) patients, which is characterized by strong Th1-type cell response with localized lesions. Generation of Th1/Th2-like effector cells, however, cannot wholly explain the polarized state of immunity in leprosy. A comprehensive understanding of the role of various regulatory T cells, such as Treg and natural killer T cells, in deciding the polarized state of T cell immunity is crucial. Interaction of these T cell subsets with effector T cells like Th1 (IFN-γ dominant), Th2 (interluekin-4 dominant), and Th17 (IL-17+) cells through various regulatory cytokines and molecules (programmed death-1/programmed death ligand-1) may constitute key events in dictating the state of immune polarization, thus controlling the clinical manifestation. Studying these important components of the adaptive immune system in leprosy patients is essential for better understanding of immune function, correlate(s) the immunity and mechanism(s) of its containment.

Keywords: Th 17; natural killer T cells; polarized immunity; programmed death-1-programmed death ligand-1; regulatory T cells.

Figure 1

The spectrum of leprosy: Ridley–Jopling classification and the relationship with host immunity. ENL, erythema nodosum leprosum or type 2 reaction.

Figure 2

Possible causes for polarized host immunity in tuberculoid type (TT) vs. lepromatous leprosy questioning the well-established Th1–Th2 paradigm. Natural killer T cells which are initial responders producing either Th1 cytokines like IFN-γ or Th2 cytokines like interluekin-4 depending on the basal cytokine response of the host. Tregs cells which are predominantly suppressive in nature and produce cytokines IL-10 and TGF-β, along with increased expression of programmed death-1 and its ligand, programmed death ligand-1 on antigen-presenting cells; these cells are found in significant numbers in lepromatous leprosy patients. Th17 or T helper 17 cells which produce the cytokines IL-17 and IL-22 demonstrate inflammatory phenotype and are, therefore, found in increased numbers in TT leprosy patients.