ExperimentalModels of Cerebral Malaria

Engwerda, Christian R.; Belnoue, Elodie; Grüner, Anne Charlotte; Rénia, Laurent

doi:10.1007/3-540-29967-x_4

Cited by 120 publications

(123 citation statements)

References 167 publications

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“…Reasons for the apparent discrepancy between our observations and those made by Voisine et al are unclear, but a potentially important difference in the studies was the genetic backgrounds of the mice used (129Sv versus C57BL/6) [32]. The genetic background of both mice and humans has an enormous influence on the magnitude and types of immune responses generated against Plasmodium [17,44,45].…”

Section: Discussioncontrasting

confidence: 80%

Type I interferons suppress CD4⁺ T‐cell‐dependent parasite control during blood‐stage Plasmodium infection

et al. 2011

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During blood‐stage Plasmodium infection, large‐scale invasion of RBCs often occurs before the generation of cellular immune responses. In Plasmodium berghei ANKA (PbA)‐infected C57BL/6 mice, CD4+ T cells controlled parasite numbers poorly, instead providing early help to pathogenic CD8+ T cells. Expression analysis revealed that the transcriptional signature of CD4+ T cells from PbA‐infected mice was dominated by type I IFN (IFN‐I) and IFN‐γ‐signalling pathway‐related genes. A role for IFN‐I during blood‐stage Plasmodium infection had yet to be established. Here, we observed IFN‐α protein production in the spleen of PbA‐infected C57BL/6 mice over the first 2 days of infection. Mice deficient in IFN‐I signalling had reduced parasite burdens, and displayed none of the fatal neurological symptoms associated with PbA infection. IFN‐I substantially inhibited CD4+ T‐bet+ T‐cell‐derived IFN‐γ production, and prevented this emerging Th1 response from controlling parasites. Experiments using BM chimeric mice revealed that IFN‐I signalled predominantly via radio‐sensitive, haematopoietic cells, but did not suppress CD4+ T cells via direct signalling to this cell type. Finally, we found that IFN‐I suppressed IFN‐γ production, and hampered efficient control of parasitaemia in mice infected with non‐lethal Plasmodium chabaudi. Thus, we have elucidated a novel regulatory pathway in primary blood‐stage Plasmodium infection that suppresses CD4+ T‐cell‐mediated parasite control.

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Section: Discussioncontrasting

confidence: 80%

Type I interferons suppress CD4⁺ T‐cell‐dependent parasite control during blood‐stage Plasmodium infection

et al. 2011

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“…21,33 Therefore, we next assessed whether anti-CD25 mAb treatment 14 days before infection affected these markers of inflammation in the brain. The number of cerebral vessels expressing either VCAM-1 or ICAM-1, as determined by immunohistochemistry, was not altered between Treg-depleted mice and controls when the latter group was sacrificed with ECM ( Figure 4, A and B), indicating that inflammation of the brain per se was not absent in mice treated with anti-CD25 mAb.…”

Section: Alterations In Cellular Recruitment To the Brain In Pba-infementioning

confidence: 99%

A Role for Natural Regulatory T Cells in the Pathogenesis of Experimental Cerebral Malaria

Amante

Stanley

Randall

et al. 2007

The American Journal of Pathology

160

172

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“…Many studies have shown that parasitemia and the subsequent potent pro-inflammatory response are essential for developing CM (Walther et al 2009). In a commonly used murine CM model, the Pb ANKA-infected C57BL/6 mice, the development of CM is associated with high levels of inflammatory mediators such as IFN-γ, TNF-α, and NO during infection (Hunt and Grau 2003;Engwerda et al 2005;Jain et al 2008;Edgerton et al 2009;). In agreement with these work, here we found that splenocytes producing pro-inflammatory mediators, such as IFN-γ-secreting Th1 cells and F4/80 + CD36 + cells, were both increased in spleen from Pb ANKA-infected mice treated with L-Arg.…”

Section: Discussionmentioning

confidence: 99%

“…Th1 cytokines play a critical role in controlling the early phase of malaria infection, but they are also associated with developing CM (Engwerda et al 2005;Nie et al 2007). A great deal of evidence about the inflammatory processes that contribute to the development of CM has been provided by the Plasmodium berghei ANKA (Pb ANKA) model (de Souza and Riley 2002;Miller et al 2002;Schofield and Grau 2005;Hansen 2012).…”

Section: Introductionmentioning

confidence: 99%

L-Arginine Exacerbates Experimental Cerebral Malaria by Enhancing Pro-Inflammatory Responses

Feng

Chen³

et al. 2015

Tohoku J. Exp. Med.

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L-Arginine (L-Arg), the substrate for nitric oxide (NO) synthase, has been used to treat malaria to reverse endothelial dysfunction in adults. However, the safety and efficacy of L-Arg remains unknown in malaria patients under the age of five, who are at the greatest risk of developing cerebral malaria (CM), a severe malaria complication. Here, we tested effects of L-Arg treatment on the outcomes of CM using a mouse model. Experimental cerebral malaria (ECM) was induced in female C57BL/6 mice infected with Plasmodium berghei ANKA, and L-Arg was administrated either prophylactically or after parasite infection. ) in the spleen. The levels of pro-inflammatory cytokines, IFN-γ and TNF-α, in splenocyte cultures were also increased by L-Arg treatment. The above changes were accompanied with a rise in the number of dendritic cells (DCs) and an increase in their maturation. However, L-Arg did not affect the population of regulatory T cells or the level of IL-10 in the spleen. Taken together, these data suggest that L-Arg may enhance the Th1 immune response, which is essential for a protective response in uncomplicated malaria but could be lethal in CM patients. Therefore, the prophylactic use of L-Arg to treat CM, based on the assumption that restoring the bioavailability of endothelial NO improves the outcome of CM, may need to be reconsidered especially for children.

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ExperimentalModels of Cerebral Malaria

Cited by 120 publications

References 167 publications

Type I interferons suppress CD4⁺ T‐cell‐dependent parasite control during blood‐stage Plasmodium infection

Type I interferons suppress CD4⁺ T‐cell‐dependent parasite control during blood‐stage Plasmodium infection

A Role for Natural Regulatory T Cells in the Pathogenesis of Experimental Cerebral Malaria

L-Arginine Exacerbates Experimental Cerebral Malaria by Enhancing Pro-Inflammatory Responses

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ExperimentalModels of Cerebral Malaria

Cited by 120 publications

References 167 publications

Type I interferons suppress CD4+ T‐cell‐dependent parasite control during blood‐stage Plasmodium infection

Type I interferons suppress CD4+ T‐cell‐dependent parasite control during blood‐stage Plasmodium infection

A Role for Natural Regulatory T Cells in the Pathogenesis of Experimental Cerebral Malaria

L-Arginine Exacerbates Experimental Cerebral Malaria by Enhancing Pro-Inflammatory Responses

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Product

Resources

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Type I interferons suppress CD4⁺ T‐cell‐dependent parasite control during blood‐stage Plasmodium infection

Type I interferons suppress CD4⁺ T‐cell‐dependent parasite control during blood‐stage Plasmodium infection