Correlation between nerve growth factor and tissue expression of IL-17 in leprosy Tinara Leila de Sousa Aar ~ ao a , Jorge Rodrigues de Sousa b , Beatriz Santos Botelho a , Hellen Thais Fuzii b , Juarez Antonio Sim ~ oes Quaresma a, b, * a Centro de Ciencias Biologicas e da Saude, Universidade do Estado do Para, Belem, Para, Brazil b Nucleo de Medicina Tropical, Universidade Federal do Para, Belem, Para, Brazil article info Article history: Received 6 October 2015 Received in revised form 11 November 2015 Accepted 19 November 2015 Available online 23 November 2015 Keywords: Nerve grown factor IL-17 Cytokines Immunopathology abstract Leprosy is a serious public health problem in peripheral and developing countries. Leprosy is a chronic infectious-contagious disease caused by the intracellular, bacillus Mycobacterium leprae, which causes tissue damage and demyelination of peripheral nerves. Recent studies have demonstrated the partici- pation of new subtype's cytokines profile in the inflammatory response of leprosy. Since nerve functions are affected by inflammatory response during the course of leprosy, changes in the production of NGF and its receptor (NGF R) may be directly associated with disability and sensory loss. Skin biopsies were collected and submitted to immunohistochemistry using specific antibodies to IL-17, NGF and NGF R. Quantitative analysis of NGF, NGFR and IL-17 immunostaining showed a significant difference between the clinical forms, with higher expression of NGF and NGFR in lepromatous leprosy and IL-17 in tuber- culoid leprosy. The present study showed that IL-17, in addition to stimulating an inflammatory response, negatively regulates the action of NGF and NGF R in the polar forms of the disease. © 2015 Elsevier Ltd. All rights reserved. 1. Introduction Leprosy is a chronic infectious-contagious disease caused by the intracellular, bacillus Mycobacterium leprae, which causes tissue damage and demyelination of peripheral nerves [1,2]. The disease is considered to be of high infectivity and low pathogenicity [3]. Leprosy is a serious public health problem in peripheral and developing countries [4]. Clinically, leprosy causes intense instability in the host immune system that reflects the spectrum of the disease. In the tuberculoid form, the patient develops a cell-mediated response characterized by the production of inflammatory cytokines. In the lepromatous form, the immune response is mediated by cells that stimulate a suppressive response. In the transient forms, the cell-mediated response oscillates between the dimorphic and dimorphic tuber- culoid and lepromatous forms [5e7]. Recent studies have demonstrated the participation of new subtypes of helper T (Th) cells producing mediators that intensify the inflammatory response in the resistant form of the disease. These cells are known as CD4þ Th17 cells, which produce cytokines such as IL-17 that stimulate the production of important chemo- kines for the recruitment of neutrophils and monocytes to the site of infection [8,9]. With respect to the defense mechanism of the organism to nerve damage, studies have shown that in inflammatory foci the immune system stimulates the production of growth factors that interfere with the differentiation and remodeling of nerve tissue. Among these factors, nerve growth factor (NGF) is an important protagonist of the response to nerve damage since it promotes the survival of primary sensory neurons, as well as of sympathetic and cholinergic neurons of the basal ganglia, and protects against neurodegeneration [10e12]. Since nerve functions are affected in leprosy patients during the course of the disease, changes in the production of NGF and its receptor (NGF R) may be directly associated with disability and sensory loss. Moreover, studies suggest that NGF and NGFR participate in the immune response by regulating the production of cytokines involved in the cell-mediated response to nerve damage [13,14]; however, these mechanisms need to be further elucidated. Therefore, by recognizing that this is an alternative under- standing of the behavior of cytokines and NGF in the spectrum of * Corresponding author. Nucleo de Medicina Tropical, Av. Generalissimo Deodoro 92, Umarizal, Belem, Para, 66055240, Brazil. E-mail address: juarez@pesquisador.cnpq.br (J.A.S. Quaresma). Contents lists available at ScienceDirect Microbial Pathogenesis journal homepage: www.elsevier.com/locate/micpath http://dx.doi.org/10.1016/j.micpath.2015.11.019 0882-4010/© 2015 Elsevier Ltd. All rights reserved. Microbial Pathogenesis 90 (2016) 64e68