Innate Immune Responses in Leprosy

Abstract

Leprosy is an infectious disease that may present different clinical forms depending on host immune response to Mycobacterium leprae. Several studies have clarified the role of various T cell populations in leprosy; however, recent evidences suggest that local innate immune mechanisms are key determinants in driving the disease to its different clinical manifestations. Leprosy is an ideal model to study the immunoregulatory role of innate immune molecules and its interaction with nervous system, which can affect homeostasis and contribute to the development of inflammatory episodes during the course of the disease. Macrophages, dendritic cells, neutrophils, and keratinocytes are the major cell populations studied and the comprehension of the complex networking created by cytokine release, lipid and iron metabolism, as well as antimicrobial effector pathways might provide data that will help in the development of new strategies for leprosy management.

Keywords: Mycobacterium leprae; autophagy; inflammasomes; innate immune responses; leprosy; skin; toll-like receptors.

Figure 1

Iron-related proteins are differentially regulated in leprosy clinical forms. Lepromatous skin lesions [lepromatous lepromatous (LL)] present a higher expression of the scavenger receptor of hemoglobin–haptoglobin complex, CD163 (upper panels), transferrin receptor 1 (TfR1, mid upper panels), the enzyme that catalyzes heme, heme-oxygenase 1 (HO-1, mid lower panels), and of the iron storage protein ferritin [ferritin light chain (FTL) lower panels]. The protein expression of CD163, TfR1, HO-1, and FTL was evaluated by immunohistochemistry. Images are representative of five independent samples from each group. Scale bars: 50 mm.

Figure 2

Beclin 1-mediated autophagy during Mycobacterium leprae infection in skin lesion-derived lepromatous macrophage. Macrophages were isolated from the skin lesion of a lepromatous leprosy patient and cultured for 18 h in full nutrient medium. Cells were fixed and immunofluorescence for Beclin 1 (magenta) and BCL2 (green) was performed. Cellular and bacterial DNA were stained with DAPI (blue). Cell and mycobacteria morphology are shown by Nomarski differential interference contrast (gray). This image shows a lepromatous tissue macrophage interacting with M. leprae. BCL2 colocalizes with Beclin 1-entrapped mycobacteria (arrowheads) allowing M. leprae survival through autophagy inhibition. The modulation of autophagy has the potential to be useful in the leprosy treatment, as well as to prevent leprosy reactional episodes. Scale bar: 20 µm.