Macrophage migration inhibitory factor contributes to immunopathogenesis during Plasmodium yoelii 17XL infection.

Macrophage migration inhibitory factor (MIF) is a cytokine recognized regulator of the inflammatory immune response associated with several immune cells that produce inflammatory cytokines such as IL-1ß, IL-6, IL-12, IL-18, and TNF-α. This study aimed to understand the effect of MIF on the immune response and pathogenesis during Plasmodium infection. Wild-type (Wt) and MIF knockout (Mif -/-) mice were intravenously infected with 1×103 Plasmodium yoelii (Py) 17XL-parasitized red blood cells. Our data showed that Py17XL-infected Wt mice died 11 days postinfection, while Mif -/- mice showed reduced parasitemia and an increase in their survival at day 11 up to 58%, importantly they succumb up to day 21 postinfection. The increased survival rate in Mif -/- mice was associated with less severe cachexia and anemia as a result of a mixed Th1/Th2 cytokine profile, high levels of IL-12, IL-17/IL-4, and IL-10 in serum; and high levels of IL-4 and IL-10, and low levels of IFN-γ in spleen cells compared to Py17XL infected Wt mice. Moreover, macrophages (Mφs) from Mif -/- mice exhibited higher concentrations of IL-10 and IL-12 and reduced levels of TNF-α and nitric oxide (NO) compared to Py17XL-infected Wt mice. These results demonstrate that MIF has an important role in regulating the immune response associated with host pathogenesis and lethality, which is relevant to consider in preventing/reducing complications in Plasmodium infections.

PD-1+ CD4 T cell immune response is mediated by HIF-1α/NFATc1 pathway after P. yoelii infection.

The morbidity and mortality of malaria are still high. Programmed cell death-1(PD-1) is an important co-inhibitory factor and CD8 T cells with PD-1 were reported to be exhausted cells. It remains unknown what the role of CD4 T cells expressing PD-1 is and what the upstream regulating molecules of PD-1 in CD4 T cells are. The C57BL/6 mice were injected with Plasmodium yoelii (P. yoelii) in this study. Expressions of PD-1, activation markers, and cytokines were tested. The differentially expressed genes between PD-1+/- CD4 T cells were detected by microarray sequencing. Western blot, chromatin immunoprecipitation (ChIP), siRNA, hypoxia inducible factor-1α (HIF-1α) inducer and inhibitor were used to explore PD-1's upstream molecules, respectively. The proportions of PD-1+ CD4 T cells increased post P. yoelii infection. PD-1+ CD4 T cells expressed more activated surface markers and could produce more cytokines. Nuclear factor of activated T cells 1 (NFATc1) was found to be a key transcription factor to induce PD-1 expression after infection. Both the inducer and the inhibitor of HIF-1α could change the expressions of NFATc1 and PD-1 in vivo and in vitro, respectively. Taken together, P. yoelii infection induced NFATc1 expression by HIF-1α. The highly expressed NFATc1 entered the nucleus and initiated PD-1 expression. PD-1+ CD4 T cells appeared to be more activated and could secrete more cytokines to regulate the host's immune responses against malaria.

Erratum: Macrophage migration inhibitor factor contributes to immunopathogenesis during Plasmodium yoelii 17XL infection.

[This corrects the article DOI: 10.3389/fcimb.2022.968422.].

Cracking Ali Baba's code.

A protein called P36 holds the key to how different species of malaria parasite invade liver cells.

Plasmodium P36 determines host cell receptor usage during sporozoite invasion.

Plasmodium sporozoites, the mosquito-transmitted forms of the malaria parasite, first infect the liver for an initial round of replication before the emergence of pathogenic blood stages. Sporozoites represent attractive targets for antimalarial preventive strategies, yet the mechanisms of parasite entry into hepatocytes remain poorly understood. Here we show that the two main species causing malaria in humans, Plasmodium falciparum and Plasmodium vivax, rely on two distinct host cell surface proteins, CD81 and the Scavenger Receptor BI (SR-BI), respectively, to infect hepatocytes. By contrast, CD81 and SR-BI fulfil redundant functions during infection by the rodent parasite P. berghei. Genetic analysis of sporozoite factors reveals the 6-cysteine domain protein P36 as a major parasite determinant of host cell receptor usage. Our data provide molecular insights into the invasion pathways used by different malaria parasites to infect hepatocytes, and establish a functional link between a sporozoite putative ligand and host cell receptors.

The study of the effective mechanism of infected host serum on the infectivity of gametocytes of Plasmodium yoelii (P.yoelii) / 中国免疫学杂志

Objective:To clarify the mechanism of crisis serum' mediated gametocyte infectivity to the mosquito vector Methods:Observing the effects of mouse serum , which was obtained 5 days after P yoelii infection (D5 serum) on gametocyte infectivity by IFA and mosquito live feeds, and the production of IFN ??TNF ??IL 4 and NO - 2 in the hosts in vivo and in vitro by ELISA and Griess reaction And to investigate the ability of malaria parasitized red blood cell extract (PRBC extract) to induce NO Results:The development of the gametocytes from mice 5 days postinfection into ookinetes were completely inhibited D5 serum was not immediate to inhibit gametocyte development, which was injected intravenously into the mice 3 days after P yoelii infection But 4 h later after injection D5 serum stimulated the increasing IFN ? and NO production and inhibited gametocyte infectivity Moreover, PRBC extract showed the ability to induce NO Conclusion:Infected host serum blocks transmission of P yoelii via a nitric oxide dependent mechanism

A COMPARATION OF ANTIMALARIAL EFFECT OF TWENTY FOUR CHEMICAL COMPOUNDS IN FOUR DAY SUPPRESIVE TEST IN MICE AND IN CULTURE / 中国药理学通报

The antimalarial effects of 24 chemical compounds on Plasmodium yoelii in mice and on Plasmodium falciparum in culture were observed . The results from both tests for most compounds are parallel or comparable, except few compounds such as Hydroxyurea and Lincomycin.What suitable methods may be used for preliminary screening of antimalarials are discussed.