Hydatidosis is a zoonotic parasitic infection that develops into cysts in the human liver, kidneys, lungs, and other organs. It is transmitted by the dog tapeworm Echinococcus granulosus in the larval stage (Agudelo Higuita et al., 2016; Ghabouli Mehrabani et al., 2014; Wen et al., 2019). Iran has an infection rate about 5 %, with nomads and rural areas reporting the highest rates (Mahmoudi et al., 2019). Infected individuals usually show no clinical symptoms, although most E. granulosus strains are capable of infecting humans (Yang et al., 2012; Agudelo Higuita et al., 2016). This suggests that host susceptibility or resistance is influenced by both the immune system and genetics, in addition to the parasite strain and its pathogenicity. Once the parasite larvae enter the human body, their surface antigens trigger the innate immune system and release pro-inflammatory factors such as IFN-γ, IL-2, and IL-12. After exposure to the antigen and cytokines, dendritic cells process the antigen and present it to T cells along with CD4 and MHC class II molecules. The Th1 signaling pathway is triggered in response to antigen presentation in the acute phase of infection when IFN-γ and IL-12 are present. The immune system fights the infection by secreting inflammatory cytokines such as IL-2, TNF-α, and IFN-γ (Wen et al., 2019; Yang et al., 2012). On the other hand, when the larvae invade, the damaged cells release cytokines that attract macrophages and other phagocytic cells to the site of infection. Through phagocytosis, these cells break down the larvae into small peptides that float in the cytosol. A pair of TAP (Transporter Associated with Antigen Processing) known as TAP1 and TAP2, transport these peptides to the endoplasmic reticulum, where they are deposited on the MHC class I groove. Human chromosome 6 houses a set of genes known as MHC molecules. Alpha-1, Alpha-2, and Alpha-3 from the MHC class I alpha chain located on the membrane of the endoplasmic reticulum. Phagocytosed parasite peptides bind to the MHC molecule via a groove formed by the binding sites for both alpha-1 and alpha-2 parts (Diaz et al., 2016; Kiper et al., 2010; Powis et al., 1993). A stable complex form when TAP binds the antigen to MHC, and MHC advances towards the cell membrane. The alpha-3 and beta-2 microglobulins of the MHC molecule enable the presentation of the antigen to the T cells. Polymorphism in TAPs, would influence the antigen presentation by MHC class I, which would affect the activation of TCD8+ cells and induce apoptosis of modified host cells. In certain regions of the TAP gene (including TAP1 codons 333 and 637 and TAP2 codons 379, 565, and 667), these mutations result in changes in the nucleotide sequence that are also found in the antigen transporter protein (TAP1, TAP2). These modifications may result in the non-presentation of some antigens by MHC class I molecules, antigen transport being disrupted, and digested foreign pathogen peptides remaining in the cell's cytoplasm (Al-Ghoury et al., 2010; Chakhtoura et al., 2007; Powis et al., 1993). Several studies have shown that TAP gene polymorphisms and single nucleotide polymorphisms can alter host immunity and affect antigen presentation. Numerous diseases, including diabetes mellitus (Jackson and Capra, 1995), inflammatory bowel disease (IBD) (Heresbach et al., 1997), and infectious diseases such as AIDS (Abitew et al., 2020), tuberculosis (Du et al., 2017), and toxoplasmosis (Goldszmid et al., 2007), are associated with the TAP gene polymorphism. There are few studies have been conducted on the relationship between TAP polymorphism and echinococcosis in some regions of the world (Ahmed and Ghaidaa, 2020; Kiper et al., 2010; Zhang et al., 2003).
There are methods in which the mutation detection system is based on polymerase chain reaction (PCR). Amplification Refractory Mutation System PCR (ARMS-PCR) is a simple technique for detecting single nucleotide polymorphisms (SNPs) and mutations. This method allows DNA amplification in the presence of the target allele by using sequence-specific PCR primers. After the ARMS reaction, the target allele is identified by gel electrophoresis of the PCR products (Little, 2001).
The aim of this study was to investigate the association between susceptibility or resistance to hydatid cyst in the Iranian population and TAP gene polymorphisms.
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