**3.** *T. spiralis* **-associated immune mechanism**

*T. spiralis* (Helminth) establishes infection which is long-lasting in the striated muscles of the host. Depending on the longevity of the host. It can persist successfully until the end of life in rodents and in higher species including humans can persist over several months to years following infection. They do not kill the host striated muscles cells during their stay, unlike some other intracellular parasites. This characteristic makes them one of the most successful symbiotic parasites [25]. Parasitic nematode *T. spiralis* completes its entire life cycle in one host and each stage of its life cycle provokes the immune system of the host differently [14, 15]. For the establishment of the life cycle successfully, this parasite with the help of its defensive mechanism manages to escape the host immune system responses. The excretory-secretory products of *T. spiralis* play a crucial role in the establishment of parasitism and modulation of host immune response to protect both host and the parasite [22]. When the host acquired the infection of *T. spiralis*, at early-stage cellular immunity of the host is inhibited but later recovery of host cellular immune function occurs, and humoral immunity starts its role in resisting the infection of *T. spiralis.* During the infection, both the cells Th1 (T helper cell) and Th2 play a major role in maintaining the immune system function. They are involved in the eradication of pathogens. When the maintenance of the host immune system disrupts it gets infected [18]. Nitric oxide (NO) is a molecule in the immune system which acts as an immunomodulator and immunotoxin. It is a gaseous molecule and has appropriate lipid membranes solubility. Without binding to any specific receptor of viruses and bacteria, it exerts lethal effects on them. NO is involved in the selective killing of parasites including infected cells and has a major role in the adult worm expulsion during *Trichinella spiralis* infection in mice (see **Figure 2**) [12].

Infection of *T. spirilis* has an immunosuppressive effect on the innate immune system of the host. Larvae release secretory antigens that elicit a protective strong immune response which is specific to invading parasites [20]. ES products reduce inflammation when parasites invade the muscle cells, modulate the host immune system response in a way to protective for both the host and the parasites. For survival inside the organism, *T. spiralis* build a unique place for their living and their niche contains a cyst or capsule composed of nurse cell (cellular components) and collagenous wall [22, 25, 26]. Both the wall and nurse cell are originated from the host, provide protection and maintenance of the parasite's metabolism respectively [14].

Macrophages play a major role in the immune response of the host against various pathogens [22]. In vitro, ES products from different phases of the life cycle of *T. spiralis* can modulate macrophage's function by inhibiting cytokine production. In chronic helminth infections, macrophages are activated by Th2 cytokines such as interleukin-4 (IL-4) and interleukin-13 (IL-13). Many immune mediator molecules are released such as IL-6, IL-12, nitric oxide (NO), and tumor necrosis factor (TNF-α) when in macrophages the signaling pathways are triggered by Th2 cytokines [22, 25, 27].
