Immune responses in liver and spleen against Plasmodium yoelii pre-erythrocytic stages in Swiss mice model

Arif Jamal Siddiqui,Jyoti Bhardwaj,Manish Goyal,Kirtika Prakash,Mohd Adnan,Mousa M Alreshidi,Mitesh Patel,Awakash Soni,Whitni Redman

doi:10.1016/j.jare.2020.02.016

Abstract

Though the immunity to malaria has been associated with cellular immune responses, the exact function of the phenotypic cell population is still unclear. This study investigated the host immune responses elicited during the pre-erythrocytic stage, post-Plasmodium yoelii sporozoite infection in Swiss mice model. For this purpose, we analyzed the dynamics of different subsets of immune cells population and cytokine levels in the hepatic mononuclear and splenic cells population during pre-erythrocytic liver-stage infection. We observed a significant reduction in the effectors immune cells population including CD8+ T cell, F4/80+ macrophage and in plasmacytoid dendritic cells (CD11c+ B220+). Interestingly, substantial down-regulation was also noted in pro-inflammatory cytokines (i.e. IFN-γ, TNF-α, IL-12, IL-2, IL-17 and iNOS), while, up-regulation of anti-inflammatory cytokines (i.e. IL-10, IL-4 and TGF-β) during asymptomatic pre-erythrocytic liver-stage infection. Collectively, this study demonstrated that during pre-erythrocytic development, Plasmodium yoelii sporozoite impaired the host activators of innate and adaptive immune responses by regulating the immune effector cells, gene expression and cytokines levels for the establishment of infection and subsequent development in the liver and spleen. The results in this study provided a better understanding of the events leading to malarial infection and will be helpful in supportive treatment and vaccine development strategy.

Highlights

Malaria is one of the highly fatal infectious diseases that cause more than 400,000 casualties and ~200 million new cases, annually [1]
The Liver stage or pre-erythrocytic stage is the first step of malaria infection that lies between sporozoite invasion of hepatocytes and merozoites released from the liver
In the present study, we aimed to investigate the immune responses against sporozoite induced primary infection and explored the dynamics of various immune cell populations and cytokine response in liver and spleen following P. yoelii sporozoites infection in Swiss albino mice model

Summary

Introduction

Malaria is one of the highly fatal infectious diseases that cause more than 400,000 casualties and ~200 million new cases, annually [1]. Sporozoites multiply asexually and release thousands of merozoites into the bloodstream [2,3]. These merozoites invade the erythrocytes and initiate the asexual blood-stage cycle (intra-erythrocytic stages), which is responsible for the clinical manifestation of malaria [4,5]. As a response to malarial infection antiparasite immune responses gets activated that can efficiently control malaria parasite infection at all development stages i.e. pre-erythrocytic, asexual stages in red cells, and sexual and mosquito stages. The role of the innate immune responses by eliciting the pro-inflammatory cytokines such as interferon c (IFNc), tumor necrosis factor a (TNFa) and interleukin-12 (IL12) during blood-stage infection was well documented. Our current knowledge regarding the innate immune responses generated during the pre-erythrocytic stages is very little

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