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

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

J Adv Res. 2020 Feb 26:24:29-41. doi: 10.1016/j.jare.2020.02.016. eCollection 2020 Jul.

Authors

Arif Jamal Siddiqui^{1

2}, Jyoti Bhardwaj³, Manish Goyal², Kirtika Prakash⁴, Mohd Adnan¹, Mousa M Alreshidi¹, Mitesh Patel⁵, Awakash Soni², Whitni Redman⁶

Affiliations

¹ Department of Biology, College of Sciences, University of Ha'il, Ha'il, Saudi Arabia.
² Division of Parasitology, CSIR-Central Drug Research Institute, Lucknow, Uttar Pradesh, India.
³ Indiana University, School of Medicine, Indianapolis, IN, United States.
⁴ Department of Obstetrics, Gynecology and Reproductive Sciences, College of Medicine, University of Vermont, VT, United States.
⁵ Bapalal Vaidya Botanical Research Centre, Department of Biosciences, Veer Narmad South Gujarat University, Surat, Gujarat, India.
⁶ Surgery Department, Division of Biomedical Research, Texas Tech University Health Sciences Center, Lubbock, TX, United States.

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.

Keywords: Immune responses; Plasmodium yoelii; Pre-erythrocytic stage; Splenic cells; Swiss mice; T cells.