Abstract
The Plasmodium parasite has to cross various immunological barriers for successful infection. Parasites have evolved mechanisms to evade host immune responses, which hugely contributes to the successful infection and transmission by parasites. One way in which a parasite evades immune surveillance is by expressing molecular mimics of the host molecules in order to manipulate the host responses. In this study, we report a Plasmodium berghei hypothetical protein, PbTIP (PbANKA_124360.0), which is a Plasmodium homolog of the human T-cell immunomodulatory protein (TIP). The latter possesses immunomodulatory activities and suppressed the host immune responses in a mouse acute graft-versus-host disease (GvHD) model. The Plasmodium berghei protein, PbTIP, is expressed on the merozoite surface and exported to the host erythrocyte surface upon infection. It is shed in the blood circulation by the activity of an uncharacterized membrane protease(s). The shed PbTIP could be detected in the host serum during infection. Our results demonstrate that the shed PbTIP exhibits binding on the surface of macrophages and reduces their inflammatory cytokine response while upregulating the anti-inflammatory cytokines such as TGF-β and IL-10. Such manipulated immune responses are observed in the later stage of malaria infection. PbTIP induced Th2-type gene transcript changes in macrophages, hinting toward its potential to regulate the host immune responses against the parasite. Therefore, this study highlights the role of a Plasmodium-released protein, PbTIP, in immune evasion using macrophages, which may represent the critical strategy of the parasite to successfully survive and thrive in its host. This study also indicates the human malaria parasite TIP as a potential diagnostic molecule that could be exploited in lateral flow-based immunochromatographic tests for malaria disease diagnosis.
Highlights
Malaria is a debilitating infectious disease in vertebrates, including humans, and is transmitted through the bites of the Plasmodium carrier Anopheles mosquitoes
We found that P. falciparum Q8I3H7 is orthologous to an uncharacterized P. berghei protein, sharing 71.9% homology
Our results indicated that the expressions of the pro-inflammatory cytokines were suppressed significantly while those of the anti-inflammatory cytokines were found significantly upregulated in the study, conveying the same notion of immunosuppression and inducing Th2 responses in macrophages upon exposure to PbTIP (Supplementary Figure S8)
Summary
Malaria is a debilitating infectious disease in vertebrates, including humans, and is transmitted through the bites of the Plasmodium carrier Anopheles mosquitoes. Natural immunity develops in a population of a malaria-endemic area by repeated Plasmodium exposure for many years through mosquito bites. It does not provide sterile protection against the disease; it is short lived and fades away quickly [3, 4]. Immune responses against blood-stage parasites are complex and possibly initiated when parasite-derived glycosylphosphatidylinositol (GPI), DNA, and metabolic products (e.g., hemozoin and uric acid) are released during the blood stage of malaria infection [5,6,7,8]. The mechanisms of host immune manipulation by the parasite remain poorly understood
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
