Chagas disease, which is caused by the flagellate parasiteTrypanosoma cruzi, affects 8–10 million people in Latin America. The disease is endemic and is characterised by acute and chronic phases that develop in the indeterminate, cardiac, and/or gastrointestinal forms. The immune response during humanT. cruziinfection is not completely understood, despite its role in driving the development of distinct clinical manifestations of chronic infection. Polymorphisms in genes involved in the innate and specific immune response are being widely studied in order to clarify their possible role in the occurrence or severity of disease. Here we review the role of classic and nonclassic MHC,KIR, and cytokine host genetic factors on the infection byT. cruziand the clinical course of Chagas disease.

Many genes includingHLA,KIR, andMICAgenes, as well as polymorphisms in cytokines have been investigated for their role in infectious disease.HLAalleles may influence not only susceptibility or resistance to leprosy, but also the course of the disease. Some combinations ofHLAandKIRmay result in negative as well as positive interactions between NK cells and infected host cells withM. leprae, resulting in activation or inhibition of NK cells and, consequently, in death of bacillus. In addition, studies have demonstrated the influence ofMICAgenes in the pathogenesis of leprosy. Specifically, they may play a role in the interaction between NK cells and infected cells. Finally, pro- and anti-inflammatory cytokines have been influencing the clinical course of leprosy. Data from a wide variety of sources support the existence of genetic factors influencing the leprosy pathogenesis. These sources include twin studies, segregation analyses, family-based linkage and association studies, candidate gene association studies, and, most recently, genome-wide association studies (GWAS). The purpose of this brief review was to highlight the importance of some immune response genes and their correlation with the clinical forms of leprosy, as well as their implications for disease resistance and susceptibility.

The aim of this study was to investigate possible associations between genetic polymorphisms ofIL17AG197A (rs2275913) andIL17FT7488C (rs763780) with Chagas Disease (CD) and/or the severity of left ventricular systolic dysfunction (LVSD) in patients with chronic Chagas cardiomyopathy (CCC). The study with 260 patients and 150 controls was conducted in the South and Southeast regions of Brazil. The genotyping was performed by PCR-RFLP. The A allele and A/A genotype ofIL17Awere significantly increased in patients and their subgroups (patients with CCC; patients with CCC and LVSD; and patients with CCC and severe LVSD) when compared to the control group. The analysis according to the gender showed that the A/A genotype ofIL17Awas more frequent in female with LVSD and mild to moderate LVSD and also in male patients with LVSD. The frequency ofIL17FT/C genotype was higher in male patients with CCC and severe LVSD and in female with mild to moderate LVSD. The results suggest the possible involvement of the polymorphisms ofIL17AandIL17Fin the susceptibility to chronic Chagas disease and in development and progression of cardiomyopathy.

MICA-129 polymorphism affects the binding affinity of MICA molecules with the NKG2D receptor and influences effector cell function. The genotype met/met was associated with the severity of left ventricular systolic dysfunction (LVSD) in patients with chronic Chagas heart disease, while the val/val genotype was associated with the absence of LVSD.

The aim of this study was to investigate the influence of killer cell immunoglobulin-like receptor (KIR) genes and their human leucocyte antigen (HLA) ligands in the susceptibility of chronic Chagas disease. This case-control study enrolled 131 serologically-diagnosed Chagas disease patients (59 men and 72 women, mean age of 60.4 ± 9.8 years) treated at the University Hospital of Londrina and the Chagas Disease Laboratory of the State University of Maringa. A control group was formed of 165 healthy individuals - spouses of patients or blood donors from the Regional Blood Bank in Maringa (84 men and 81 women, with a mean age of 59.0 ± 11.4 years). Genotyping of HLA and KIR was performed by PCR-SSOP. KIR2DS2-C1 in the absence of KIR2DL2 (KIR2DS2⁺/2DL2^-/C1⁺) was more frequent in Chagas patients (P = 0.020; Pc = 0.040; OR = 2.14) and, in particular, those who manifested chronic chagasic cardiopathy—CCC (P = 0.0002; Pc = 0.0004; OR = 6.64; 95% CI = 2.30–18.60) when compared to the control group, and when CCC group was compared to the patients without heart involvement (P = 0.010; Pc = 0.020; OR = 3.97). The combination pair KIR2DS2⁺/2DL2^-/KIR2DL3⁺/C1⁺ was also positively associated with chronic chagasic cardiopathy. KIR2DL2 and KIR2DS2 were related to immunopathogenesis in Chagas disease. The combination of KIR2DS2 activating receptor with C1 ligand, in the absence of KIR2DL2, may be related to a risk factor in the chronic Chagas disease and chronic chagasic cardiopathy. Chagas disease is an infection caused by the haemoflagellate protozoan Trypanosoma cruzi. It is one of the most important public health problems in Latin America, and was first described by Carlos Justiniano Ribeiro das Chagas, a Brazilian physician and scientist, in 1909. It is mostly vector-borne transmitted to humans by contact with faeces of triatomine bugs. The World Health Organization estimates that about 6 to 7 million people are currently infected with T. cruzi worldwide. The disease is characterised by acute and chronic phases. The immune response during disease development is crucial for protection because immunological imbalances can lead to heart and digestive tract lesions in chagasic patients. In this work we analysed the role of receptors of immune cells known as Natural Killer cells (killer cell immunoglobulin-like receptor—KIR) and their ligands (Human leukocyte antigens—HLA) in chagasic patients compared to healthy individuals. The uncontrolled activation of NK cells can lead to tissue damage, which, in turn, leads to the development of serious chronic illness. We found that KIR-HLA complex may be related to a risk factor in the chronic Chagas disease and chronic chagasic cardiopathy.