Interleukin-33 exerts pleiotropic immunoregulatory effects in response to Plasmodium berghei ANKA (PbA) infection in mice

Abstract

Objective: To determine the involvement and the modulatory effects of IL-33 during Plasmodium berghei ANKA (PbA) infection. Methods: PbA infection in male ICR mice was utilized as a model of malaria. Systemically circulating IL-33 levels were determined in blood plasma by enzyme-linked immunosorbent assay (ELISA). After 24 hours post-inoculation of PbA, recombinant IL-33 and ST2, and antibodies against IL-33 and IgG treatments were administered daily for 3 days. Tissue expression and localization of IL-33 were assessed in organs generally affected by malaria via immunohistochemistry. Moreover, histopathological examination was performed to assess the effects of the treatments. Results: The levels of systemic IL-33 were elevated at the critical phase of PbA infection. Likewise, immunohistochemical analysis revealed a significant upregulation of IL-33 expression at the critical phase in the brain, lungs, and spleen of PbA-infected mice as compared to healthy controls. Treatment with IL-33 protected against experimental cerebral malaria development and reduced pathological features in the brain and lungs of the PbA-infected mice. Conclusions: A potential critical role and involvement of IL-33 in PbA infection may hint at the resolution of immunopathological sequelae associated with malaria.

Keywords

Plasmodium berghei ANKA / Malaria / IL-33 / Immunology / Immunotherapy

Acknowledgments

We would like to convey our gratitude to the Institutional Animal Care and Use Committee of Universiti Putra Malaysia for the animal handling facility provided by the Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, and Malaysia Ministry of Higher Education for the research funding under the Fundamental Research Grant Scheme.

Conflict of interest statement

The authors declare that they have no conflict of interest.

Funding

The research was supported by the Fundamental Research Grant Scheme (FRGS) from the Malaysia Ministry of Higher Education (FRGS/1/2016/SKK10/UPM/02/1).

Data availability statement

The data supporting the findings of this study are available from the corresponding authors upon request.

Authors’ contributions

MFARI conceptualized the work, carried out literature search, experimental studies and data acquisition, and wrote the original draft. RB conceptualized the work, sought for funding, supervised the project and edited the manuscript. RBO, RAM, MAA, CNMT, SPP, YYK, and CVK reviewed and edited the manuscript. MGL made critical revision and contributed to the final version of the manuscript.

Publisher’s note

The Publisher of the Journal remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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