Related Experiment Video
Updated: Sep 7, 2025
CRISPR/Cas9 Gene Editing to Make Conditional Mutants of Human Malaria Parasite P. falciparum
Published on: September 18, 2018
CCR6 expression reduces mouse survival upon malarial challenge with Plasmodium berghei NK65 strain
Eduardo Lani Volpe da Silveira1, Urvashi Rai1, Vivian Bonezi2
1New York University School of Medicine, Department of Pathology, Michael Heidelberg Division of Immunology, New York, NY, United States of America.
Background:
It has been demonstrated that proteins expressed by liver-stage Plasmodium parasites can inhibit the translocation of transcription factors to the nucleus of different cells. This process would hinder the expression of immune genes, such as the CCL20 chemokine.
Objective:
Since CCR6 is the only cognate receptor for CCL20, we investigated the importance of this chemokine-receptor axis against rodent malaria.
Methods:
CCR6-deficient (KO) and wild-type (WT) C57BL/6 mice were challenged with Plasmodium berghei (Pb) NK65 sporozoites or infected red blood cells (iRBCs). Liver parasitic cDNA, parasitemia and serum cytokine concentrations were respectively evaluated through reverse transcription-polymerase chain reaction (RT-PCR), staining thin-blood smears with Giemsa solution, and enzyme-linked immunosorbent assay (ELISA).
Findings:
Although the sporozoite challenges yielded similar liver parasitic cDNA and parasitemia, KO mice presented a prolonged survival than WT mice. After iRBC challenges, KO mice kept displaying higher survival rates as well as a decreased IL-12 p70 concentration in the serum than WT mice.
Conclusion:
Our data suggest that malaria triggered by PbNK65 liver- or blood-stage forms elicit a pro-inflammatory environment that culminates with a decreased survival of infected C57BL/6 mice.
Insights
Malaria parasites can suppress immune genes. Blocking the CCL20-CCR6 interaction in mice improved survival against Plasmodium berghei, suggesting a therapeutic target for malaria.
Area of Science:
- Immunology
- Infectious Diseases
- Malariology
Background:
- Plasmodium parasite proteins can inhibit immune gene expression by blocking nuclear transcription factor translocation.
- This inhibition affects crucial immune mediators like the CCL20 chemokine.
Purpose of the Study:
- Investigate the role of the CCL20-CCR6 chemokine-receptor axis in rodent malaria.
- Determine the impact of CCR6 deficiency on Plasmodium berghei infection outcomes.
Main Methods:
- Utilized CCR6-deficient (KO) and wild-type (WT) C57BL/6 mice challenged with Plasmodium berghei (Pb) NK65.
- Assessed liver parasitic load via RT-PCR, parasitemia by blood smear analysis, and serum cytokine levels using ELISA.
Main Results:
- CCR6 KO mice showed prolonged survival compared to WT mice after both sporozoite and infected red blood cell (iRBC) challenges.
- KO mice exhibited higher survival rates and reduced IL-12 p70 serum concentrations following iRBC challenge.
Conclusions:
- Malaria infection by PbNK65 induces a pro-inflammatory environment in C57BL/6 mice.
- This inflammatory response is associated with decreased survival, highlighting the potential therapeutic significance of the CCL20-CCR6 axis.
More Related Videos
08:23Phenotypic Analysis of Rodent Malaria Parasite Asexual and Sexual Blood Stages and Mosquito Stages
Published on: May 30, 2019
09:13Author Spotlight: Identifying Compensatory Pathways in Malaria Parasites Containing Hypomorphic Allele of Essential Protein Kinases
Published on: November 22, 2024