September 2015 Vol. 3 No.9

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Original Research Article

Expression of Physiologic Biomolecules following Anti-Malarial Cytokine-CpG Motif Oligodeoxynucleotide Gene Therapy

Barasa Mustafa^1,2,3*, Shaviya Nathan³, Wamalwa Ronald³, Mambo Fidelis³, Okoth Patrick⁴, Omedo Asaba Robin³, Reuben Rutto², Kagasi Ambogo Esther⁵, Mutai Charles³, Sowayi Alubokho George³, Ozwara Suba Hastings⁵, Ng’ang’a Waithera Zipporah¹ and Anjili Omukhango Christopher²
 

¹The Institute of Tropical Medicine and Infectious Diseases (ITROMID), College of Health Sciences (COHES) – Jomo Kenyatta University of Agriculture and Technology (JKUAT), Nairobi, Kenya
²The Center for Biotechnology Research and Development (CBRD), Kenya Medical Research Institute (KEMRI), Nairobi, Kenya
³The Department of Medical Laboratory Sciences (MLS), Masinde Muliro University of Science and Technology (MMUST), Kakamega, Kenya
⁴The Department of Biological Sciences, Masinde Muliro University of Science and Technology (MMUST)
⁵The Tropical and Infectious Diseases Department, Institute of Primate Research (IPR), Nairobi, Kenya

*Corresponding Author’s Email: mustrech@yahoo.com; mbarasa@mmust.ac.ke

Accepted September 21, 2015

Abstract

According to latest estimates, there were 198 million cases of malaria worldwide in 2013, with 82% of these cases occurring in Africa. There were approximately 584,000 malaria deaths worldwide. The outcome of infection with Plasmodia parasites is determined by the activities of various biomolecules, cytokines and other host-specific factors. Plasmodia parasites evade immunity and modulate immune systems to their advantage thereby exacerbating infection and disease. When combined in therapy, immunostimulatory unmethylated CpG motif oligodeoxynucleotides (ODNs) synergise with cytokines in the promotion of anti-parasitic mechanisms providing effective protection in various cases. The CpG ODNs enhance immune activities through ligation to plasmacytoid dendritic cell (pDC) Toll-like receptors (TLRs) such as TLR-9 and they activate both pDCs and B-cells, while cytokines modulate cellular behaviour. By altering cellular functionality, the cytokine-CpG ODN immunotherapy combination can alter the expression of physiologic factors and this can influence disease outcomes including severity of infection with malaria parasites. It was previously unclear how physiologic biomolecules like matrix metalloproteinases (MMPs) and angiopoietins (ANGPTs) could be influenced by the coincidental introduction of recombinant cytokines and CpG ODNs during malaria. This project studied cytokine-CpG motif ODN co-inoculation in BALB/c mice infected with P. berghei ANKA strain. Two BALB/c mice groups infected with virulent blood stage P. berghei ANKA strain parasites were given immunotherapeutic cytokine and CpG ODN combinations for five consecutive days while six other control groups with different treatments were included for comparison. The mice were monitored daily for clinical symptoms and parasitaemia development from day 1 postinfection. At ten days postinfection, all mice were humanely sacrificed for the extraction of EDTA-treated blood and plasma for measuring various physiologic factors. Results unraveled cytokine-CpG-based gene therapy as an enhancer of anti-Plasmodial activities accompanied by elevations in adiponectin, ANGPT1, neuropilin-1(NRP-1) and cyclooxygenase-2 (Cox-2) and delevations in ANGPT2, MMP-8 and MMP-9. These physiologic outcomes, which are largely agreeable with data from other studies, favour further investigations on combinatorial cytokine-CpG ODN gene therapy for potential inclusion into preventative and therapeutic anti-malarial interventions.

Key Words: BALB/c Mice, Cytokines, CpG Motif ODN, Malaria, P. berghei ANKA, Physiologic Biomolecules.