Browsing by Subject "Sporozoites"

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    Impact of chemoprophylaxis immunisation under halofantrine (CPS-HF) drug cover in Plasmodium yoelii Swiss mice malaria model
    (Institute of Parasitology, Biology Centre of the Academy of Sciences, 2022-02-03) Siddiqui, Arif Jamal; Bhardwaj, Jyoti; Hamadou, Walid Sabri; Goyal, Manish; Jahan, Sadaf; Ashraf, Syed Amir; Jamal, Arshad; Sharma, Pankaj; Sachidanandan, Manojkumar; Badraoui, Riadh; Snoussi, Mejdi; Adnan, Mohd; Medicine, School of Medicine
    In the present study, we have investigated the role of antimalarial drug halofantrine (HF) in inducing the sterile protection against challenges with sporozoites of the live infectious Plasmodium yoelii (Killick-Kendrick, 1967) in Swiss mice malaria model. We observed that during the first to third sequential sporozoite inoculation cycles, blood-stage patency remains the same in the control and chemoprophylaxis under HF drug cover (CPS-HF) groups. However, a delayed blood-stage infection was observed during the fourth and fifth sporozoite challenges and complete sterile protection was produced following the sixth sporozoite challenge in CPS-HF mice. We also noticed a steady decline in liver stage parasite load after 3th to 6th sporozoite challenge cycle in CPS-HF mice. CPS-HF immunisation results in a significant up-regulation of pro-inflammatory cytokines (IFN-γ, TNF-α, IL-12 and iNOS) and down-regulation of anti-inflammatory cytokines (IL-10 and TGF-β) mRNA expression in hepatic mononuclear cells (HMNC) and spleen cells in the immunised CPS-HF mice (after 6th sporozoite challenge) compared to control. Overall, our study suggests that the repetitive sporozoite inoculation under HF drug treatment develops a strong immune response that confers protection against subsequent challenges with sporozoites of P. yoelii.
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    The Plasmodium eukaryotic initiation factor-2α kinase IK2 controls the latency of sporozoites in the mosquito salivary glands
    (Rockefeller University Press, 2010) Zhang, Min; Fennell, Clare; Ranford-Cartwright, Lisa; Sakthivel, Ramanavelan; Gueirard, Pascale; Meister, Stephan; Caspi, Anat; Doerig, Christian; Nussenzweig, Ruth S.; Tuteja, Renu; Sullivan, William J., Jr.; Roos, David S.; Fontoura, Beatriz M. A.; Ménard, Robert; Winzeler, Elizabeth A.; Nussenzweig, Victor; Pharmacology and Toxicology, School of Medicine
    Sporozoites, the invasive form of malaria parasites transmitted by mosquitoes, are quiescent while in the insect salivary glands. Sporozoites only differentiate inside of the hepatocytes of the mammalian host. We show that sporozoite latency is an active process controlled by a eukaryotic initiation factor-2alpha (eIF2alpha) kinase (IK2) and a phosphatase. IK2 activity is dominant in salivary gland sporozoites, leading to an inhibition of translation and accumulation of stalled mRNAs into granules. When sporozoites are injected into the mammalian host, an eIF2alpha phosphatase removes the PO4 from eIF2alpha-P, and the repression of translation is alleviated to permit their transformation into liver stages. In IK2 knockout sporozoites, eIF2alpha is not phosphorylated and the parasites transform prematurely into liver stages and lose their infectivity. Thus, to complete their life cycle, Plasmodium sporozoites exploit the mechanism that regulates stress responses in eukaryotic cells.