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外文期刊>Journal of King Saud University
>Complement protein C1q binds soluble antigens of Leishmania major (SLA) via the globular head region, activates the classical pathway, and modulates macrophage immune response
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Complement protein C1q binds soluble antigens of Leishmania major (SLA) via the globular head region, activates the classical pathway, and modulates macrophage immune response
Leishmania species cause a range of moderate to severe diseases affecting cutaneous to visceral regions, thus having a great impact on morbidity and mortality. Leishmania is initially dealt with by human innate immune system immediately after its entry into the body, primarily by the complement system, one of the most potent humoral immune mechanisms that link innate and adaptive immunity. Complement can be activated via all its three pathways on the surface of Leishmania to varying degrees; however, it is considered that the classical pathway is the first to respond due to a lag phase preceding the alternative pathway activation. The present study illustrated that the recognition molecule, C1q bound to soluble leishmania antigens (SLA) derived fromL. majorvia its domains and activates the classical pathway. This was confirmed in complement consumption assay where SLA was able to induce only ~22% haemolysis of sensitized cells. Moreover, this study showed that recombinant individual head regions of C1q chains bind differentially to SLA while interaction studies with substitution mutants revealed that C1q-SLA binding relied on charge-charge interaction. When macrophage-like cell line, THP-1, was challenged with SLA in the presence of human C1q, it downregulated a number of cytokine and chemokine response considerably; the effects were mostly suppressive of Th1 immune response, suggesting that the requirements for potent adjuvants in SLA-mediated vaccine strategies.
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