The Role of TLR-4 on the Mapkinases Signaling Pathways of Inflammatory Responses against Recombinant BCG Malaria Vaccine Candidate
Malaria, a life-threatening disease caused by Plasmodium parasites which have developed resistance to all anti-malaria drugs on the background resistance of the mosquito vector to insecticides, necessitating more intense search for an effective vaccine. A recombinant BCG (rBCG) vaccine candida...
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| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Umaru Musa Yar'adua University, Katsina, Nigeria
2018-12-01
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| Series: | UMYU Journal of Microbiology Research |
| Subjects: | |
| Online Access: | https://ujmr.umyu.edu.ng/index.php/ujmr/article/view/226 |
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| Summary: |
Malaria, a life-threatening disease caused by Plasmodium parasites which have developed resistance to all anti-malaria drugs on the background resistance of the mosquito vector to insecticides, necessitating more intense search for an effective vaccine. A recombinant BCG (rBCG) vaccine candidate expressing the merozoite surface protein 1C (MSP-1C) of Plasmodium falciparum was developed in our laboratory, which generated robust innate and adaptive immune responses that pointed to the likelihood of the role of Toll- like receptor-4 (TLR-4). This study analysed the role TLR-4 attachment of the rBCG to macrophages in eliciting the observed immune responses. Mice (n = 6 per group) were immunised with PBS-T80, parent BCG or rBCG in the presence or absence of a TLR-4 inhibitor; TAK-242 and the effects of TLR-4 on the expression of c-Jun N-terminal kinases 1 and 2 (JNK1/2) and extracellular signal–regulated kinases 1 and
2 (ERK1/2) which are involved in the signalling pathway were analysed through western blot on macrophages harvested from the mice peritoneum. The results obtained showed a significant increase in the expression of the MAPKinases in the group immunised with rBCG compared to BCG and PBS-T80 immunised groups. There was significant inhibition of the JNK1/2 and ERK1/2 expression in the presence of TAK-242 signifying, for the first time, the role of TLR-4 in the phosphorylation of both JNK1/2 and ERK1/2 in the immune response against the vaccine candidate expressing the MSP-1C of P. falciparum. This study highlighted the role of TLR-4 in the phosphorylation of ERK1/2 and JNK1/2 in the immune response against recombinant BCG malaria vaccine candidate
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| ISSN: | 2616-0668 2814-1822 |