Abstract
BackgroundKiller-cell immunoglobulin-like receptors (KIRs) are a group of regulatory molecules able to activate or inhibit natural killer cells upon interaction with human leukocyte antigen (HLA) class I molecules. Combinations of KIR and HLA may contribute to the occurrence of different immunological and clinical responses to infectious diseases. Leprosy is a chronic neglected disease, both disabling and disfiguring, caused mainly by Mycobacterium leprae. In this case–control study, we examined the influence of KIRs and HLA ligands on the development of multibacillary leprosy.Methodology/Principal findingsGenotyping of KIR and HLA genes was performed in 264 multibacillary leprosy patients and 518 healthy unrelated controls (238 healthy household contacts and 280 healthy subjects). These are unprecedented results in which KIR2DL2/KIR2DL2/C1/C2 and KIR2DL3/2DL3/C1/C1 indicated a risk for developing lepromatous and borderline leprosy, respectively. Concerning to 3DL2/A3/A11+, our study demonstrated that independent of control group (contacts or healthy subjects), this KIR receptor and its ligand act as a risk factor for the borderline clinical form.Conclusions/SignificanceOur finding suggests that synergetic associations of activating and inhibitory KIR genes may alter the balance between these receptors and thus interfere in the progression of multibacillary leprosy.
Highlights
Natural killer (NK) cells are crucial components of the innate immune system and provide defence against viral and microbial infections, cancer and other forms of cell stress [1]
The individuals considered most affected and associated with a major risk for developing leprosy are household contacts with an intimate relation to patients living in crowded households
We chose the contacts as one of our control groups, since they are more exposed to infection compared to the general population
Summary
Natural killer (NK) cells are crucial components of the innate immune system and provide defence against viral and microbial infections, cancer and other forms of cell stress [1]. The activity of NK cells requires interaction between a KIR and certain HLA class I ligands expressed on the surface of the cells. This interaction may protect unaltered cells from destruction or stimulate NK cell function [12,13,14]. The cytotoxic function of NK cells on target cells is regulated through the balance between activating and inhibitory signals that results from the interaction of KIRs and their HLA class I ligands [15,16]. Leprosy is a chronic neglected disease, both disabling and disfiguring, caused mainly by Mycobacterium leprae In this case–control study, we examined the influence of KIRs and HLA ligands on the development of multibacillary leprosy
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