Transcriptional Modulation of the Host Immunity Mediated by Cytokines and Transcriptional Factors in Plasmodium falciparum-Infected Patients of North-East India

Abstract

Complications due to malaria are caused mostly by host immunological responses. Plasmodium falciparum subverts host immunity by various strategies, including modulation in the host immune responses by regulating cytokines. The transcriptional alterations of major cytokines and immunoregulators were analyzed in this study through gene expression profiling in clinically defined subgroups of P. falciparum patients. Malaria patients were included from Dhalai district hospital of Tripura with uncomplicated malaria (UC) and severe malaria (SM) and healthy controls from endemic and non-endemic areas of India. qPCR gene expression analysis was performed for all factors and they were grouped into three clusters based on their altered expressions. The first cluster was downregulated with an increased parasitic burden which included T-BET, GATA3, EOMES, TGF-β, STAT4, STAT6 and cytokines IFN-γ, IL-12, IL-4, IL-5, and IL-13. RANTES, IL-8, CCR8, and CXCR3 were decreased in the SM group. The second cluster was upregulated with severity and included TNF-α, IL-10, IL-1β and IL-7. PD-1 and BCL6 were increased in the SM group. The third cluster comprised of NF-κB and was not altered. The level of perforin was suppressed while GrB expression was elevated in SM. P. falciparum malaria burden is characterized by the modulation of host immunity via compromization of T cell-mediated responses and suppression of innate immune-regulators.

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