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.
Highlights
IntroductionLife-threatening disease [1] and continues to be a public health problem worldwide with approximately 219 million infected cases worldwide in 2017 by the World Health
Malaria is a multifactorial, life-threatening disease [1] and continues to be a public health problem worldwide with approximately 219 million infected cases worldwide in 2017 by the World HealthOrganization [2]
Gender distribution between the groups was markedly discriminated with a higher percentage of males affected by severe malaria
Summary
Life-threatening disease [1] and continues to be a public health problem worldwide with approximately 219 million infected cases worldwide in 2017 by the World Health. P. falciparum, which is known to cause severe malaria, is responsible for about half the malaria burden in India [3]. P. falciparum malaria is widespread in rural areas of the country. Endemicity is stratified differently for different parts of the country. North-eastern states (Arunachal Pradesh, Assam, Manipur, Meghalaya, Mizoram, Nagaland, Sikkim, and Tripura) of the country account for only 4% of the country’s population, yet contribute to 10% P. falciparum cases [4]. The study state, has reported 12,390 malaria cases in 2018, most of them being P. falciparum [3]
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