Murine AIDS protects mice against experimental cerebral malaria: down-regulation by interleukin 10 of a T-helper type 1 CD4+ cell-mediated pathology.

Eckwalanga, Michel; Marussig, Myriam; Tavares, Marisa Dias; Bouanga, Jean Claude; Hulier, Elisabeth; Pavlovitch, J. H.; Minóprio, Paola; Portnoı̈, Denis; Rénia, Laurent; Mazier, Dominique

doi:10.1073/pnas.91.17.8097

Cited by 52 publications

(43 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…IL-12 induces downstream cytokines that mediate the immune response during Plasmodium infection. IL-12 induces IL-10 production (80), and IL-10 plays a major role in preventing ECM (28,33,34,76). Due to the immunosuppressive nature of IL-10, the induction of IL-10 could have prevented the localization of T cells to the brain.…”

Section: Anka-infected Il-12␤rmentioning

confidence: 99%

“…IL-10 suppresses a Th1 response and has been shown in multiple studies to play a major role in preventing ECM (28,33,34,75). To investigate whether STAg-induced protection against ECM requires IL-10, we infected IL-10 Ϫ/Ϫ mice with P. berghei ANKA and treated mice with STAg after 24 h. STAg treatment was just as effective in wild-type (wt) and IL-10 Ϫ/Ϫ mice, as evidenced by similar percent survivals (Fig.…”

Section: Stag Treatment Alone and Stag Treatment Of P Berghei-infecmentioning

confidence: 99%

“…Additionally, investigating the immune response during coinfection, either with other Plasmodium spp. (28,29), helminths (30)(31)(32)(33), or LP-BM5, the murine leukemia virus that induces murine AIDS (30,34), has allowed the identification of immune components necessary for protection from ECM.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Toxoplasma gondii Upregulates Interleukin-12 To Prevent Plasmodium berghei-Induced Experimental Cerebral Malaria

et al. 2014

View full text Add to dashboard Cite

A chronic infection with the parasite Toxoplasma gondii has previously been shown to protect mice against subsequent viral, bacterial, or protozoal infections. Here we have shown that a chronic T. gondii infection can prevent Plasmodium berghei ANKA-induced experimental cerebral malaria (ECM) in C57BL/6 mice. Treatment with soluble T. gondii antigens (STAg) reduced parasite sequestration and T cell infiltration in the brains of P. berghei-infected mice. Administration of STAg also preserved blood-brain barrier function, reduced ECM symptoms, and significantly decreased mortality. STAg treatment 24 h post-P. berghei infection led to a rapid increase in serum levels of interleukin 12 (IL-12) and gamma interferon (IFN-␥). By 5 days after P. berghei infection, STAg-treated mice had reduced IFN-␥ levels compared to those of mock-treated mice, suggesting that reductions in IFN-␥ at the time of ECM onset protected against lethality. Using IL-10-and IL-12␤R-deficient mice, we found that STAg-induced protection from ECM is IL-10 independent but IL-12 dependent. Treatment of P. berghei-infected mice with recombinant IL-12 significantly decreased parasitemia and mortality. These data suggest that IL-12, either induced by STAg or injected as a recombinant protein, mediates protection from ECM-associated pathology potentially through early induction of IFN-␥ and reduction in parasitemia. These results highlight the importance of early IL-12 induction in protection against ECM.

show abstract

Section: Anka-infected Il-12␤rmentioning

confidence: 99%

Section: Stag Treatment Alone and Stag Treatment Of P Berghei-infecmentioning

confidence: 99%

See 1 more Smart Citation

Toxoplasma gondii Upregulates Interleukin-12 To Prevent Plasmodium berghei-Induced Experimental Cerebral Malaria

et al. 2014

View full text Add to dashboard Cite

show abstract

“…In addition, anti-TNF-␣ and anti-IFN-␥ antibodies appear able to abolish the onset of cerebral malaria (17,19). Of note, IL-10 has been proposed to downregulate Th1 cytokine production, resulting in a lower incidence of cerebral symptoms in mice coinfected with Plasmodium berghei and IL-10-stimulating LP-BM5 murine leukemia virus (10).…”

mentioning

confidence: 99%

Serum Levels of the Proinflammatory Cytokines Interleukin-1 Beta (IL-1β), IL-6, IL-8, IL-10, Tumor Necrosis Factor Alpha, and IL-12(p70) in Malian Children with SeverePlasmodium falciparumMalaria and Matched Uncomplicated Malaria or Healthy Controls

et al. 2004

View full text Add to dashboard Cite

Inflammatory cytokines play an important role in human immune responses to malarial disease. However, the role of these mediators in disease pathogenesis, and the relationship between host protection and injury remains unclear. A total of 248 cases of severe Plasmodium falciparum malaria among children aged 3 months to 14 years residing in Bandiagara, Mali, were matched to cases of uncomplicated malaria and healthy controls. Using modified World Health Organization criteria for defining severe malaria, we identified 100 cases of cerebral malaria (coma, seizure, and obtundation), 17 cases of severe anemia (hemoglobin, <5 g/dl), 18 cases combined cerebral malaria with severe anemia, and 92 cases with hyperparasitemia (asexual trophozoites, >500,000/mm3). Significantly elevated levels (given as geometric mean concentrations in picograms/milliliter) of interleukin-6 (IL-6; 485.2 versus 54.1; P = <0.001), IL-10 (1,099.3 versus 14.1; P = <0.001), tumor necrosis factor alpha (10.1 versus 7.7; P = <0.001), and IL-12(p70) (48.9 versus 31.3; P = 0.004) in serum were found in severe cases versus healthy controls. Significantly elevated levels of IL-6 (485.2 versus 141.0; P = <0.001) and IL-10 (1,099.3 versus 133.9; P = <0.001) were seen in severe malaria cases versus uncomplicated malaria controls. Cerebral malaria was associated with significantly elevated levels of IL-6 (754.5 versus 311.4; P = <0.001) and IL-10 (1,405.6 versus 868.6; P = 0.006) compared to severe malaria cases without cerebral manifestations. Conversely, lower levels of IL-6 (199.2 versus 487.6; P = 0.03) and IL-10 (391.1 versus 1,160.9; P = 0.002) were noted in children with severe anemia compared to severe malaria cases with hemoglobin at >5 g/dl. Hyperparasitemia was associated with significantly lower levels of IL-6 (336.6 versus 602.1; P = 0.002). These results illustrate the complex relationships between inflammatory cytokines and disease in P. falciparum malaria.

show abstract

“…In humans, a class I MHC allele as well as a class II MHC haplotype have been associated with protection from severe forms of malaria (3). In mouse CM models that mimick only partially the neuropathology in humans (4), the immune system plays an active deleterious role, as evidenced by the protective effect of immunosuppressive treatments (5)(6)(7). T␣␤ cells, both CD4 ϩ and CD8 ϩ subpopulations, are necessary for the development of experimental CM as shown in nude, knockout, and T cell-depleted mice (6, 8 -12).…”

mentioning

confidence: 99%

A Profound Alteration of Blood TCRB Repertoire Allows Prediction of Cerebral Malaria

Collette

Bagot

Ferrandiz

et al. 2004

The Journal of Immunology

View full text Add to dashboard Cite

Cerebral malaria (CM) is one of the severe complications of Plasmodium infection. In murine models of CM, Tαβ cells have been implicated in the neuropathogenesis. To obtain insights into the TCRB repertoire during CM, we used high throughput CDR3 spectratyping and set up new methods and software tools to analyze data. We compared PBL and spleen repertoires of mice infected with Plasmodium berghei ANKA that developed CM (CM+) or not (CM−) to evidence modifications of the TCRB repertoire associated with neuropathology. Using distinct statistical multivariate methods, the PBL repertoires of CM+ mice were found to be specifically altered. This alteration is partly due to recurrently expanded T cell clones. Strikingly, alteration of the PBL repertoire can be used to distinguish between CM+ and CM−. This study provides the first ex vivo demonstration of modifications of Tαβ cell compartment during CM. Finally, our original approach for deciphering lymphocyte repertoires can be transposed to various pathological conditions.

show abstract

Murine AIDS protects mice against experimental cerebral malaria: down-regulation by interleukin 10 of a T-helper type 1 CD4+ cell-mediated pathology.

Cited by 52 publications

References 43 publications

Toxoplasma gondii Upregulates Interleukin-12 To Prevent Plasmodium berghei-Induced Experimental Cerebral Malaria

Toxoplasma gondii Upregulates Interleukin-12 To Prevent Plasmodium berghei-Induced Experimental Cerebral Malaria

Serum Levels of the Proinflammatory Cytokines Interleukin-1 Beta (IL-1β), IL-6, IL-8, IL-10, Tumor Necrosis Factor Alpha, and IL-12(p70) in Malian Children with SeverePlasmodium falciparumMalaria and Matched Uncomplicated Malaria or Healthy Controls

A Profound Alteration of Blood TCRB Repertoire Allows Prediction of Cerebral Malaria

Contact Info

Product

Resources

About