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NOT Open Access | Development of Plasmodium-specific liver resident-memory CD8(+) T cells after heat-killed sporozoite immunization in mice

January 27, 2021 - 10:03 -- NOT Open Access
Ghilas S, Enders MH, May R, Holz L, Fernandez-Ruiz D, Cozijnsen A, Mollard V, Cockburn IA, McFadden GI, Heath WR, Beattie L
Eur J Immunol. 2021 Jan 23

Malaria remains a major cause of mortality in the world, and an efficient vaccine is the best chance of reducing the disease burden. Vaccination strategies for the liver stage of disease that utilise injection of living radiation-attenuated sporozoites (RAS) confer sterile immunity, which is mediated by CD8+ memory T cells, with liver-resident memory T cells (TRM ) being particularly important. We have previously described a TCR transgenic mouse, termed PbT-I, where all CD8+ T cells recognize a specific peptide from Plasmodium. PbT-I form liver TRM cells upon RAS injection and are capable of protecting mice against challenge infection.

NOT Open Access | Artemisinin inhibits TLR4 signaling by targeting co-receptor MD2 in microglial BV-2 cells and prevents lipopolysaccharideinduced blood brain barrier leakage in mice

January 19, 2021 - 16:11 -- NOT Open Access
Zhang T, Zhang X, Lin C, Wu S, Wang F, Wang H, Wang Y, Peng Y, Hutchinson MR, Li H, Wang X
J Neurochem. 2021 Jan 16

Artemisinin and its derivatives have been the frontline drugs for treating malaria. In addition to the antiparasitic effect, accumulating evidence shows that artemisinins can alleviate neuroinflammatory responses in the central nervous system (CNS). However, the precise mechanisms underlying their anti-neuroinflammatory effects are unclear. Herein we attempted to delineate the molecule target of artemisinin in microglia. In vitro protein intrinsic fluorescence titrations and saturation transfer difference (STD)-NMR showed the direct binding of artemisinin to TLR4 co-receptor MD2.

Adaptive immune responses mediated age-related Plasmodium yoelii 17XL and 17XNL infections in 4 and 8-week-old BALB/c mice

January 12, 2021 - 15:10 -- Open Access
Wang QB, Du YT, Liu F, Sun XD, Sun X, Chen G, Pang W, Cao YM
BMC Immunol. 2021 Jan 11;22(1):6

It is important to expound the opposite clinical outcomes between children and adulthood for eradicate malaria. There remains unknown about the correlation between adaptive immune response and age-related in malaria.

NOT Open Access | Age reduces resistance and tolerance in malaria-infected mice

December 30, 2020 - 13:32 -- NOT Open Access
Sorci G, Léchenault-Bergerot C, Faivre B
Infect Genet Evol. 2020 Dec 25:104698

Once infected, hosts can rely on two strategies to cope with parasites: fight them (resist the infection) or minimize the damage they induce (tolerate the infection). While there is evidence that aging reduces resistance, how tolerance varies as hosts become old has been barely studied. Here, we used a rodent malaria parasite (Plasmodium yoelii) to investigate whether 2- and 12-month old house mice differ in their capacity to resist and tolerate the infection.

BCG Provides Short-Term Protection from Experimental Cerebral Malaria in Mice

December 16, 2020 - 09:31 -- Open Access
Witschkowski J, Behrends J, Frank R, Eggers L, von Borstel L, Hertz D, Mueller AK, Schneider BE
Vaccines (Basel). 2020 Dec 9;8(4):E745

Clinical and experimental evidence suggests that the tuberculosis vaccine BCG offers protection against unrelated pathogens including the malaria parasite. Cerebral malaria (CM) is the most severe complication associated with Plasmodium falciparum infection in humans and is responsible for most of the fatalities attributed to malaria. We investigated whether BCG protected C57BL/6 mice from P. berghei ANKA (PbA)-induced experimental CM (ECM).

A history of juvenile mild malaria exacerbates chronic stress-evoked anxiety-like behavior, neuroinflammation, and decline of adult hippocampal neurogenesis in mice

November 19, 2020 - 13:43 -- Open Access
Guha SK, Sarkar I, Patgaonkar M, Banerjee S, Mukhopadhyay S, Sharma S, Pathak S, Vaidya VA
J Neuroimmunol. 2020 Nov 15;348:577363

Children residing in high malaria transmission regions are particularly susceptible to malaria. This early-life window is also a critical period for development and maturation of the nervous system, and inflammatory insults during this period may evoke a persistent increase in vulnerability for psychopathology. We employed a two-hit model of juvenile mild malaria and a two-week chronic unpredictable mild stress (CUMS) regime, commencing 60 days post-parasite clearance, to assess whether a history of juvenile infection predisposed the mice towards mood-related behavioral alterations and neurocognitive deficits.

Not Open Access | Comparative antimalarial, toxicity and mito-protective effects of Diospyros mespiliformis Hochst. ex A. DC. and Mondia whitei (Hook.f.) Skeels on Plasmodium berghei infection in mice

November 18, 2020 - 11:41 -- NOT Open Access
Olanlokun JO, Bodede O, Prinsloo G, Olorunsogo OO
J Ethnopharmacol. 2020 Nov 12:113585

Diospyros mespiliformis Hochst. ex A. DC. and Mondia whitei (Hook.f.) Skeels are traditionally used in Africa for the treatment of malaria. However, scientific evidence to substantiate this folkloric claim and their effects on liver mitochondria during malaria treatment have not been reported.

Aim of the study

This study investigated the efficacy of D. mespiliformis and M. whitei against chloroquine-sensitive and resistant strains of malarial parasites in mice. It also investigated the toxicity and protection against cellular organelles like mitochondria.

NOT Open Access | Methnaridine is an orally bioavailable, fast-killing and long-acting antimalarial agent that cures Plasmodium infections in mice

September 23, 2020 - 09:36 -- NOT Open Access
Wang W, Yao J, Chen Z, Sun Y, Shi Y, Wei Y, Zhou H, Yu Y, Li S, Duan L
Br J Pharmacol. 2020 Sep 22

Malaria is one of the deadliest diseases in the world. Novel chemotherapeutic agents are urgently required to combat the widespread Plasmodium resistance to frontline drugs. Here, we report the discovery of a novel benzonaphthyridine antimalarial, methnaridine, which was identified using a structural optimization strategy.

A Plasmodium cysteine protease required for efficient transition from the liver infection stage

September 23, 2020 - 08:55 -- Open Access
Putrianti ED, Schmidt-Christensen A, Heussler V, Matuschewski K, Ingmundson A
PLoS Pathog. 2020 Sep 21;16(9):e1008891

The transitions between developmental stages are critical points in the Plasmodium life cycle. The development of Plasmodium in the livers of their mammalian hosts bridges malaria transmission and the onset of clinical symptoms elicited by red blood cell infection. The egress of Plasmodium parasites from the liver must be a carefully orchestrated process to ensure a successful switch to the blood stage of infection.

NOT Open Access | Humanized Mice and the Rebirth of Malaria Genetic Crosses

September 15, 2020 - 15:07 -- NOT Open Access
Vendrely KM, Kumar S, Li X, Vaughan AM
Trends Parasitol. 2020 Sep 2:S1471-4922(20)30192-6

The first experimental crosses carried out with the human malaria parasite Plasmodium falciparum played a key role in determining the genetic loci responsible for drug resistance, virulence, invasion, growth rate, and transmission.


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