KIR-HLA combinations and susceptibility to tuberculosis

Abstract

Introduction: Tuberculosis (TB), caused by Mycobacterium Tuberculosis (Mtb), with more than nine million new cases and almost two million deaths in each year is a worldwide important public health problem. Generally, human immune responses prevent Mtb spread, and the infection remains in a latent state. Both, innate and adaptive immune responses are involved against TB. However, the role of the innate immunity is still not well clear. Through mechanisms such as cytotoxicity and cytokine production, Natural Killer (NK) cells are among the first line of defence against infections. The ability of NK cytotoxicity is related to Killer cell Immunoglobulin-like Receptors (KIR) found on the cell surface. The KIR gene cluster is located on chromosome 19 within the leukocyte receptor complex. KIR proteins act as receptors that recognize Human Leukocyte Antigen (HLA) class I molecules and are directly involved in the activation and inhibition of NK cells. KIRs and their HLA class I ligands contribute to the pathogenesis of diverse kinds of diseases. The genetic imbalance of inhibitory and activating KIRs may be the key factor, which influences the pathogenesis of TB. However, the Role of KIR-HLA in determining susceptibility to TB is a topic of debatable. This review summarizes the major features of these genes and discusses how they may be involved in TB pathogenesis.