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plasmodium yoelii

Non-lethal Plasmodium yoelii infection drives complex patterns of Th2-type host immunity and mast cell-dependent bacteremia

September 23, 2020 - 09:09 -- Open Access
Céspedes N, Donnelly E, Garrison S, Haapanen L, Van De Water J, Luckhart S
Infect Immun. 2020 Sep 21:IAI.00427-20

Malaria strongly predisposes to bacteremia, which is associated with sequestration of parasitized red blood cells and increased gastrointestinal permeability. The mechanisms underlying this disruption are poorly understood. Here we evaluated the expression of factors associated with mast cell activation and malaria-associated bacteremia in a rodent model. C57BL/6J mice were infected with Plasmodium yoelii yoelli 17XNL and blood and tissues were collected over time to assay for circulating levels of bacterial 16S DNA, IgE, mast cell protease 1 (Mcpt-1) and Mcpt-4, Th1 and Th2 cytokines as well as patterns of ileal mastocytosis and intestinal permeability.

Contributions of IFN-γ and granulysin to the clearance of Plasmodium yoelii blood stage

September 15, 2020 - 10:59 -- Open Access
Hojo-Souza NS, de Azevedo PO, de Castro JT, Teixeira-Carvalho A, Lieberman J, Junqueira C, Gazzinelli RT
PLoS Pathog. 2020 Sep 10;16(9):e1008840

P. vivax-infected Retics (iRetics) express human leukocyte antigen class I (HLA-I), are recognized by CD8+ T cells and killed by granulysin (GNLY) and granzymes. However, how Plasmodium infection induces MHC-I expression on Retics is unknown. In addition, whether GNLY helps control Plasmodium infection in vivo has not been studied. Here, we examine these questions using rodent infection with the P. yoelii 17XNL strain, which has tropism for Retics.

Exhausted CD4(+) T Cells during Malaria Exhibit Reduced mTORc1 Activity Correlated with Loss of T-bet Expression

September 15, 2020 - 10:16 -- Open Access
Villegas-Mendez A, Khandelwal G, McGowan LM, Dookie RS, Haley MJ, George C, Sims D, Lord GM, Sinclair LV, Jenner RG, Couper KN
J Immunol. 2020 Sep 15;205(6):1608-1619

CD4+ T cell functional inhibition (exhaustion) is a hallmark of malaria and correlates with impaired parasite control and infection chronicity. However, the mechanisms of CD4+ T cell exhaustion are still poorly understood. In this study, we show that Ag-experienced (Ag-exp) CD4+ T cell exhaustion during Plasmodium yoelii nonlethal infection occurs alongside the reduction in mammalian target of rapamycin (mTOR) activity and restriction in CD4+ T cell glycolytic capacity. We demonstrate that the loss of glycolytic metabolism and mTOR activity within the exhausted Ag-expCD4+ T cell population during infection coincides with reduction in T-bet expression.

Bacillus sphaericus exposure reduced vector competence of Anopheles dirus to Plasmodium yoelii by upregulating the Imd signaling pathway

September 8, 2020 - 12:34 -- Open Access
Yu S, Wang P, Qin J, Zheng H, Wang J, Liu T, Yang X, Wang Y
Parasit Vectors. 2020 Sep 5;13(1):446

Vector control with Bacillus sphaericus (Bs) is an effective way to block the transmission of malaria. However, in practical application of Bs agents, a sublethal dose effect was often caused by insufficient dosing, and it is little known whether the Bs exposure would affect the surviving mosquitoes’ vector capacity to malaria.

Memory CD73+IgM+ B cells protect against Plasmodium yoelii infection and express Granzyme B

September 8, 2020 - 12:00 -- Open Access
Parra M, Weitner M, Yang A, Akue A, Liu X, Schmidt T, Allman WR, Akkoyunlu M, Derrick SC
PLoS One. 2020 Sep 4;15(9):e0238493

To better understand anti-malaria protective immune responses, we examined the cellular mechanisms that govern protective immunity in a murine Plasmodium yoelii 17X NL (PyNL) re-infection model. Initially, we confirmed that immune B cells generated during a primary PyNL infection were largely responsible for protection from a second PyNL infection.

Potential and Limitations of Cross-Protective Vaccine against Malaria by Blood-Stage Naturally Attenuated Parasite

July 15, 2020 - 15:01 -- Open Access
Imai T, Suzue K, Ngo-Thanh H, Shimokawa C, Hisaeda H
Vaccines (Basel). 2020 Jul 11; 8(3):E375

Human malaria vaccine trials have revealed vaccine efficacy but improvement is still needed. In this study, we aimed to re-evaluate vaccination with blood-stage naturally attenuated parasites, as a whole-organism vaccine model against cross-strain and cross-species malaria, to establish a better vaccination strategy. C57BL/6 mice controlled blood-stage Plasmodium yoelii 17XNL (PyNL) within 1 month of infection, while mice with a variety of immunodeficiencies demonstrated different susceptibilities to PyNL, including succumbing to hyperparasitemia.

Metabolic constraints on the B cell response to malaria

July 8, 2020 - 15:01 -- Open Access
Rodda LB, Pepper M
Nat Immunol. 2020 Jul;21(7):722-724

When confronted with a new pathogen, the humoral immune system works to clear the pathogen and prevent a future infection. How pathogen clearance and memory formation are balanced when Plasmodium yoelii infects mice, a model of human malaria, is unclear. In this issue of Nature Immunology, Vijay et al. suggest that plasmablasts may act as a competitive sink for l-glutamine, thereby constraining the germinal center (GC) response1.

Not Open Access | The E3 ubiquitin ligase MARCH1 regulates antimalaria immunity through interferon signaling and T cell activation

July 2, 2020 - 13:23 -- NOT Open Access
Wu J, Xia L, Su XZ, et al.
Proc Natl Acad Sci U S A. 2020 Jun 30:202004332

Malaria infection induces complex and diverse immune responses. To elucidate the mechanisms underlying host–parasite interaction, we performed a genetic screen during early (24 h) Plasmodium yoelii infection in mice and identified a large number of interacting host and parasite genes/loci after transspecies expression quantitative trait locus (Ts-eQTL) analysis.

Novel malaria antigen Plasmodium yoelii E140 induces antibody-mediated sterile protection in mice against malaria challenge

May 19, 2020 - 14:30 -- Open Access
Smith EC, Limbach KJ, Aguiar JC, et al.
PLoS ONE 15(5): e0232234

Only a small fraction of the antigens expressed by malaria parasites have been evaluated as vaccine candidates. A successful malaria subunit vaccine will likely require multiple antigenic targets to achieve broad protection with high protective efficacy. Here we describe protective efficacy of a novel antigen, Plasmodium yoelii (Py) E140 (PyE140), evaluated against P. yoelii challenge of mice.

NOT Open Access | Vancomycin improves Plasmodium yoelii malaria parasite in vitro liver stage cultures by controlling Elizabethkingia anophelis, a bacterium in the microbiome of lab-reared Anopheles mosquitoes

May 6, 2020 - 15:01 -- NOT Open Access
Shears MJ, Murphy SC
Mol Biochem Parasitol. 2020 Apr 30:111279

Studies of Plasmodium sporozoites and liver stages require dissection of Anopheles mosquitoes to obtain sporozoites for experiments. Sporozoites from the rodent parasite P. yoelii are routinely used to infect hepatocytes for liver stage culture, but sometimes these cultures become contaminated. Using standard microbiological techniques, a single colony type of Gram-negative rod-shaped bacteria was isolated from contaminated cultures.


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