Neutrophils in Leprosy

Abstract

Leprosy is an infectious disease caused by the intracellular bacillus Mycobacterium leprae that mainly affects the skin and peripheral nerves. One of the most intriguing aspects of leprosy is the diversity of its clinical forms. Paucibacillary patients are characterized as having less than five skin lesions and rare bacilli while the lesions in multibacillary patients are disseminated with voluminous bacilli. The chronic course of leprosy is often interrupted by acute episodes of an inflammatory immunological response classified as either reversal reaction or erythema nodosum leprosum (ENL). Although ENL is considered a neutrophilic immune-complex mediated condition, little is known about the direct role of neutrophils in ENL and leprosy disease overall. Recent studies have shown a renewed interest in neutrophilic biology. One of the most interesting recent discoveries was that the neutrophilic population is not homogeneous. Neutrophilic polarization leads to divergent phenotypes (e.g., a pro- and antitumor profile) that are dynamic subpopulations with distinct phenotypical and functional abilities. Moreover, there is emerging evidence indicating that neutrophils expressing CD64 favor systemic inflammation during ENL. In the present review, neutrophilic involvement in leprosy is discussed with a particular focus on ENL and the potential of neutrophils as clinical biomarkers and therapeutic targets.

Keywords: Mycobacterium leprae; erythema nodosum leprosum; inflammation; leprosy; neutrophils.

Figure 1

Skin lesions of ENL patient. Image from Leprosy Laboratory collection.

Figure 2

(A) Histopathological aspects of ENL skin lesions. (B) High power showing foamy macrophages and neutrophil infiltrate. (C) High power showing a collection of neutrophils (microabscess) in deep dermis. (D) Necrotizing ENL, Epidermal ulceration with vasculitis. Hematoxylin and eosin staining (scale bars: 100 μm). Images from Leprosy Laboratory collection.

Figure 3

ENL skin lesions present neutrophils expressing CD64. The protein expression of CD64 on neutrophil (MPO⁺ cells) was evaluated by immunofluorescence. Skin lesion was stained for CD64 (red), myeloperoxidase (MPO; green), and nuclei (DAPI; blue). Images are representative of three independent samples of ENL patients. Co-localized areas of MPO⁺CD64⁺ cells were identified with arrows. The regulation of neutrophil CD64 expression has the potential to be useful in the ENL treatment, as well as to prevent ENL reactional episodes. Scale bars: 10 μm. Images from Leprosy Laboratory collection.