Leprosy is a chronic infectious disease caused by Mycobacterium leprae. According to official reports from 121 countries across five WHO regions, there were 213 899 newly diagnosed cases in 2014. Although leprosy affects the skin and peripheral nerves, it can present across a spectrum of clinical and histopathological forms that are strongly influenced by the immune response of the infected individuals. These forms comprise the extremes of tuberculoid leprosy (TT), with a M. leprae-specific Th1, but also a Th17, response that limits M. leprae multiplication, through to lepromatous leprosy (LL), with M. leprae-specific Th2 and T regulatory responses that do not control M. leprae replication but rather allow bacterial dissemination. The interpolar borderline clinical forms present with similar, but less extreme, immune biases. Acute inflammatory episodes, known as leprosy reactions, are complications that may occur before, during or after treatment, and cause further neurological damages that can cause irreversible chronic disabilities. This review discusses the innate and adaptive immune responses, and their interactions, that are known to affect pathogenesis and influence the clinical outcome of leprosy.Electronic supplementary materialThe online version of this article (doi:10.1186/s40249-016-0229-3) contains supplementary material, which is available to authorized users.

Introduction: Leprosy is a chronic disease that affects skin and peripheral nerves. Disease complications include reactional episodes and physical impairment. One World Health Organization (WHO) goal of leprosy programs is to decrease the number of grade 2 impairment diagnoses by 2015. This study aims to evaluate clinical factors associated with the occurrence of leprosy reactions and physical impairment in leprosy patients. Methods: We conducted a retrospective study of data from medical records of patients followed in two important centers for the treatment of leprosy in Aracaju, Sergipe, Brazil, from 2005 to 2011. We used the chi-square test to analyze associations between the following categorical variables: gender, age, operational classifi cation, clinical forms, leprosy reactions, corticosteroid treatment, and physical impairment at the diagnosis and after cure. Clinical variables associated with multibacillary leprosy and/or reactional episodes and the presence of any grade of physical impairment after cure were evaluated using the logistic regression model. Results: We found that men were more affected by multibacillary forms, reactional episodes, and grade 2 physical impairment at diagnosis. Leprosy reactions were detected in a total of 40% of patients and all were treated with corticosteroids. However, physical impairment was observed in 29.8% of the patients analyzed at the end of the treatment and our multivariate analysis associated a low dose and short period of corticosteroid treatment with persistence of physical impairments. Conclusions: Physical impairment should receive an increased attention before and after treatment, and adequate treatment should be emphasized.

It is well established that helper T cell responses influence resistance or susceptibility to Mycobacterium leprae infection, but the role of more recently described helper T cell subsets in determining severity is less clear. To investigate the involvement of Th17 cells in the pathogenesis of leprosy, we determined the immune profile with variant presentations of leprosy. Firstly, IL-17A, IFN-γ and IL-10 were evaluated in conjunction with CD4 T cell staining by confocal microscopy of lesion biopsies from tuberculoid (TT) and lepromatous leprosy (LL) patients. Secondly, inflammatory cytokines were measured by multiplex assay of serum samples from Multibacillary (MB, n = 28) and Paucibacillary (PB, n = 23) patients and household contacts (HHC, n = 23). Patients with leprosy were also evaluated for leprosy reaction occurrence: LR+ (n = 8) and LR- (n = 20). Finally, peripheral blood mononuclear cells were analysed by flow cytometry used to determine the phenotype of cytokine-producing cells. Lesions from TT patients were found to have more CD4 IL-17A cells than those from LL patients. Higher concentrations of IL-17A and IL-1β were observed in serum from PB than MB patients. The highest serum IFN-γ concentrations were, however, detected in sera from MB patients that developed leprosy reactions (MB LR ). Together, these results indicate that Th1 cells were associated with both the PB presentation and also with leprosy reactions. In contrast, Th17 cells were associated with an effective inflammatory response that is present in the PB forms but were not predictive of leprosy reactions in MB patients.

Leprosy is a chronic infection caused by Mycobacterium leprae. It affects the skin and peripheral nerves and can cause irreversible chronic disabilities. The worldwide registered number of cases in 2009 was 213,036. This review discusses clinical aspects of the disease, including leprosy reactions and neuronal damage, as well as immunological and immunogenetic aspects influencing disease susceptibility and outcome. The cardinal signs of leprosy are skin lesions with altered sensation, thickened peripheral nerves, and presence of alcohol acid-resistant bacilli in skin biopsy or lymph. Confirmatory examinations include (1) bacteriological examination, which allows patients' classification into two operational groups, multibacillary (MB) and paucibacillary (PB); and (2) histopathological examination, which permits stratification in different clinical forms. These clinical forms differ not only by histopathology but also according to the host's immune response to M. leprae. These forms comprise the extremes of (1) tuberculoid leprosy (TT), with a specific Th1 response and control of M. leprae multiplication; (2) lepromatous leprosy (LL) without Th1 response and preserved Th2 response; and (3) the interpolar clinical forms, borderline tuberculoid (BT), borderline borderline (BB), borderline lepromatous (BL), and indeterminate form (IL). Appropriate treatment is based on smear examination or the number of lesions at diagnosis. In the evolution of leprosy, acute inflammation, known as reactions, may occur during or after treatment. These reactions are classified into two main types: the type I reaction or reversal reaction (RR), and the type II reaction or erythema nodosum leprosum (ENL). The role of innate immune response to control the infection is supported by immunological and genetic studies. Drug Dev Res 72:509-527, 2011.