Similarly, during acute VL, human PBMCs failed to develop IL-1 in response to the stimulation of the antigen (Elliott et?al., 1989). Cytokine Production and T Cell Polarization in VL The cellular immune response bridges the gap between innate and adaptive immune responses. viz. IFN-, IL-2, IL-12, and TNF- play an important role during protection, while some other cytokines viz. IL-10, IL-6, IL-17, TGF-, as well as others are associated with disease progression. Therefore, comprehensive knowledge of cytokine response and their conversation with various immune cells is very crucial to determine appropriate immunotherapies for VL. Here, we have discussed the role of cytokines involved in VL disease progression or host protection in different animal models and humans that will determine the clinical end result of VL and open the path for the development of quick and accurate diagnostic tools as well as therapeutic interventions against VL. These species are obligate intracellular parasites that mostly target the visceral organs of the host. The clinical manifestations of the disorder show the severity of the disease, which could be highly fatal in its advanced stage. VL is usually a vector-borne contamination communicated by female sandflies; it is known as a disease of poor people because of its high prevalence in developing countries or malnourished populations around the world. It mainly affects the tropical and subtropical countries. Symptoms of VL include enlargement of the liver and spleen, fever, extreme excess weight loss, hypergammaglobulinemia, as well as the low count of RBCs, WBCs, and platelets. The Rabbit Polyclonal to MRIP parasite resides within the hostile environment of the macrophages of the spleen, liver, and bone marrow of the host. The immune system of the host is also compromised during disease progression. You will find 50,000 to 90,000 new cases of VL reported worldwide annually, while the mortality rate in untreated VL patients is over 95% (https://www.who.int/news-room/fact-sheets/detail/leishmaniasis). The establishment of VL contamination is mainly associated with host immune response where T helper type 1 (Th1) and T helper type 2 (Th2) cytokines play an important role in VL (Saha et?al., 2007; Mondal et?al., 2010; Nyln and Gautam, 2010). The Th1 response is known to protect from VL infection, whereas the Th2 immune response is responsible for parasite growth and disease progression. Th1 type immune response is mainly associated with the production of interleukin (IL)-12, interferon- (IFN-), nitric oxide (NO), and reactive oxygen species (ROS) (Kaye and Scott, 2011), while the secretion of Interleukin (IL)-4, IL-10 and transforming growth factor-beta (TGF-) is mainly associated with Th2 immune response. Several other cytokines viz IL-3, IL-5, IL-6, IL-8, IL-9, IL-13, IL-15, IL-18, IL-23, and IL-27 also play a critical role during disease progression or Mogroside V protection ( Table 1 ). (Elliott et?al., 1989; Barral-Netto et?al., 1991; Milano et?al., 2002; Chamizo et?al., 2005; Murray et?al., 2006b; St?ger et?al., 2006; de Lima et?al., 2007; Maroof and Kaye, 2008; Murray, 2008; Zhu et?al., 2010; Menezes-Souza et?al., 2011; Ghosh et?al., 2013b; Hajilooi et?al., 2015; Prez-Cabezas et?al., 2016; Quirino et?al., 2016; Ramos et?al., 2016; Costa and Gomes, 2020; Lamberet et?al., 2020; Moravej et?al., 2020) Table 1 Role of Mogroside V various cytokines in experimental models and humans for the management of VL. crude or purified gp63 antigen stimulationBoth protection and disease progression(Ho et?al., 1992; Kurtzhals et?al., 1994)IFN-Activates macrophages and monocytes to release oxygen radicals and TNF-, IL-l, and IL-6 secretionHost protection(Hart et?al., 1989)TGF-Macrophage deactivation, suppress healing responses and avoid host parasite clearanceDisease progression(Bogdan et?al., 1991)TNF-Activation of effector immune responseHost protection(Zwingenberger et?al., 1991)IL-6Inhibits production of TNF- in the early stage of infectionDisease progression(Costa et?al., 2013; Dos Santos et?al., 2016)IL-17Affects neutrophils function, reduces apoptosis, induces the production of pro-inflammatory cytokines and tissue damaging molecules at inflammatory fociDisease progression(Dragon et?al., 2008)IL-27Increases the Th1 response and dampens the production of IL-17 mediated neutrophil infiltrationHost protection(Quirino et?al., 2016)IL-1Impaired production of IL-1 from human PBMCs with results in a self-healing chronic contamination. In addition, cytokine phenotypes exhibited in the mouse model by viscerotropic are not characteristic of a Th2-type response (Papadopoulou et?al., 2002). Apart from mice, the hamster model for VL contamination is widely accepted for immunological studies (Melby et?al., 2001; Garg and Dube, 2006; Aslan et?al., 2013). The cytokine response in the hamster is usually pretty much much like humans against VL contamination. Currently, the Syrian Golden hamster is usually accepted worldwide to test numerous prophylactic and therapeutic measures. A major drawback of visceral models is that only large doses of antimony in the primary visceral disease model will eliminate known lesions (the hamster model). The model has also been used in vaccination research (Sharma et?al., 2003; Sharma et?al., 2004). However, the molecular mechanisms for this high degree Mogroside V of vulnerability are uncertain, and you will find limited immunological studies applicable to this model due to the lack of available reagents. Since all rodent models have the disadvantage of having different drug metabolisms and pharmacokinetics from humans, secondary.
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