The Contribution of Co-signaling Pathways to Anti-malarial T Cell Immunity.

Rebecca Faleiro,Michelle Wykes,Joshua M Horne-Debets,Deshapriya S Karunarathne

doi:10.3389/fimmu.2018.02926

Rebecca Faleiro, Michelle Wykes + Show 2 more

Open Access

https://doi.org/10.3389/fimmu.2018.02926

Copy DOI

Abstract

Plasmodium spp., the causative agent of malaria, caused 212 million infections in 2016 with 445,000 deaths, mostly in children. Adults acquire enough immunity to prevent clinical symptoms but never develop sterile immunity. The only vaccine for malaria, RTS,S, shows promising protection of a limited duration against clinical malaria in infants but no significant protection against severe disease. There is now abundant evidence that T cell functions are inhibited during malaria, which may explain why vaccine are not efficacious. Studies have now clearly shown that T cell immunity against malaria is subdued by multiple the immune regulatory receptors, in particular, by programmed cell-death-1 (PD-1). Given there is an urgent need for an efficacious malarial treatment, compounded with growing drug resistance, a better understanding of malarial immunity is essential. This review will examine molecular signals that affect T cell-mediated immunity against malaria.

Highlights

Malaria is a disease caused by parasites of the Plasmodium spp. of which there are six species that infect humans: P. falciparum, P. vivax, P. ovale, P. malariae, P. knowlesi, and P. cynomolgi
CD28 was found to be crucial for development of both polyclonal as well as specific antibody responses against malaria, as mice deficient in CD28 had a severe deficit in Ig-production by B cells by day 7 post-infection with P. chabaudi compared to WT mice [38]
Antibody-mediated blockade of cytotoxic T-lymphocyte associated antigen-4 (CTLA-4) during P. berghei-infection in experimental cerebral malaria (ECM)-resistant BALB/c mice resulted in higher levels of T cell activation, enhanced IFN-γ production, increased intravascular arrest of both parasitised erythrocytes and CD8+ T cells to the brain, and augmented incidence of ECM [36]

Summary

Introduction

Malaria is a disease caused by parasites of the Plasmodium spp. of which there are six species that infect humans: P. falciparum, P. vivax, P. ovale, P. malariae, P. knowlesi, and P. cynomolgi. Combined blockade of PD-L1 and Lymphocyte-activation gene 3 (LAG3) immune inhibitory molecules accelerated clearance of non-lethal P. yoelii bloodstage malaria by improving CD4+ T cell functions and increasing antibody titres [33]. CD28 was found to be crucial for development of both polyclonal as well as specific antibody responses against malaria, as mice deficient in CD28 had a severe deficit in Ig-production by B cells by day 7 post-infection with P. chabaudi compared to WT mice [38].

Results

Conclusion