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plasmodium yoelii

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

September 15, 2020 - 10:16 -- Open Access
Author(s): 
Villegas-Mendez A, Khandelwal G, McGowan LM, Dookie RS, Haley MJ, George C, Sims D, Lord GM, Sinclair LV, Jenner RG, Couper KN
Reference: 
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
Author(s): 
Yu S, Wang P, Qin J, Zheng H, Wang J, Liu T, Yang X, Wang Y
Reference: 
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
Author(s): 
Parra M, Weitner M, Yang A, Akue A, Liu X, Schmidt T, Allman WR, Akkoyunlu M, Derrick SC
Reference: 
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
Author(s): 
Imai T, Suzue K, Ngo-Thanh H, Shimokawa C, Hisaeda H
Reference: 
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
Author(s): 
Rodda LB, Pepper M
Reference: 
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
Author(s): 
Wu J, Xia L, Su XZ, et al.
Reference: 
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
Author(s): 
Smith EC, Limbach KJ, Aguiar JC, et al.
Reference: 
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
Author(s): 
Shears MJ, Murphy SC
Reference: 
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.

Plasmodium yoelii 17XL infection modified maturation and function of dendritic cells by skewing Tregs and amplificating Th17

April 10, 2020 - 16:44 -- Open Access
Author(s): 
Chen G, Du JW, Nie Q, Du YT, Liu SC, Liu DH, Zhang HM, Wang FF
Reference: 
BMC Infect Dis. 2020 Apr 6;20(1):266

Emerging data has suggested that Tregs, Th17, Th1 and Th2 are correlated with early immune mechanisms by controlling Plasmodium infection. Plasmodium infection appeared to impair the antigen presentation and maturation of DCs, leading to attenuation of specific cellular immune response ultimately. Hence, in this study, we aim to evaluate the relevance between DCs and Tregs/Th17 populations in the process and outcomes of infection with Plasmodium yoelii 17XL (P.y17XL).

NOT Open Access | The C-terminal region of the Plasmodium yoelii microgamete surface antigen PyMiGS induces potent anti-malarial transmission-blocking immunity in mice

March 17, 2020 - 12:55 -- NOT Open Access
Author(s): 
Tachibana M, Baba M, Takashima E, Tsuboi T, Torii M, Ishino T
Reference: 
Vaccine Volume 38, Issue 15, 30 March 2020, Pages 3129-3136

Malaria transmission-blocking vaccines (TBVs) aim to inhibit parasite fertilization or further development within the mosquito midgut. Because TBV-immunized individuals reduce the transmission of malaria parasites to mosquito vectors, TBVs could serve as a promising strategy to eliminate malaria.

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