Critical role of the neutrophil-associated high-affinity receptor for IgE in the pathogenesis of experimental cerebral malaria

Porcherie, Adeline; Mathieu, C.; Péronet, Roger; Schneider, Elke; Claver, Julien; Commère, Pierre‐Henri; Kiefer-Biasizzo, Hélène; Karasuyama, Hajime; Milon, Geneviève; Dy, Michel; Kinét, Jean-Pierre; Louis, Jacques; Blank, Ulrich; Mécheri, Salaheddine

doi:10.1084/jem.20110845

Cited by 90 publications

(92 citation statements)

References 51 publications

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“…Therefore, as seen with allergy, not all patients should have the same probability of developing SM. This consideration could help to reconcile our results with those obtained in a murine model whose allergic susceptibility remains to be determined (32). Further studies are required to identify the determinants of basophil sensitization, such as mosquito bites (D. Aldebert, unpublished data), allergen sensitization, or helminth coinfection, in areas of malaria endemicity, but this new field of investigation has already provided additional keys for a better understanding of malaria immunopathogenesis.…”

Section: Discussionmentioning

confidence: 73%

Enhanced Basophil Reactivities during Severe Malaria and Their Relationship with the Plasmodium falciparum Histamine-Releasing Factor Translationally Controlled Tumor Protein

et al. 2012

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ABSTRACTRecent studies suggest shared pathogenic pathways during malaria and allergy. Indeed, IgE, histamine, and the parasite-derivedPlasmodium falciparumhistamine-releasing factor translationally controlled tumor protein (PfTCTP) can be found at high levels in serum from patients experiencing malaria, but their relationship with basophil activation remains unknown. We recruitedP. falciparum-infected patients in Senegal with mild malaria (MM;n= 19) or severe malaria (SM;n= 9) symptoms and healthy controls (HC;n= 38). Levels of serum IgE, PfTCTP, and IgG antibodies against PfTCTP were determined by enzyme-linked immunosorbent assays (ELISA). Basophil reactivities to IgE-dependent and -independent stimulations were measuredex vivousing fresh blood by looking at the expression level of the basophil activation marker CD203c with flow cytometry. Unstimulated basophils from MM had significantly lower levels of CD203c expression compared to those from HC and SM. After normalization on this baseline level, basophils from SM showed an enhanced reactivity to calcimycin (A23187) and hemozoin. Although SM reached higher median levels of activation after anti-IgE stimulation, great interindividual differences did not allow the results to reach statistical significance. When primed with recombinant TCTP before anti-IgE, qualitative differences in terms of a better ability to control excessive activation could be described for SM. IgE levels were very high in malaria patients, but concentrations in MM and SM were similar and were not associated with basophil responses, which demonstrates that the presence of IgE alone cannot explain the various basophil reactivities. Indeed, PfTCTP could be detected in 32% of patients, with higher concentrations for SM. These PfTCTP-positive patients displayed significantly higher basophil reactivities to any stimulus. Moreover, the absence of anti-PfTCTP IgG was associated with higher responses in SM but not MM. Our results show an association between basophil reactivity and malaria severity and suggest a pathogenic role for plasmodial PfTCTP in the induction of this allergy-like mechanism.

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Section: Discussionmentioning

confidence: 73%

Enhanced Basophil Reactivities during Severe Malaria and Their Relationship with the Plasmodium falciparum Histamine-Releasing Factor Translationally Controlled Tumor Protein

et al. 2012

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“…In contrast, Porcherie et al reported that mast cells and basophils are not involved in experimental cerebral malaria after infection with P. berghei ANKA (33). Based on these findings and the known abilities of IL-3 to influence mast cell and basophil growth and function, the role of endogenous IL-3 in regulating the numbers of splenic mast cells during P. berghei NK65 infection were examined.…”

Section: Resultsmentioning

confidence: 99%

Interleukin-3-Deficient Mice Have Increased Resistance to Blood-Stage Malaria

et al. 2014

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The contribution of interleukin-3 (IL-3), a hematopoietic growth factor and immunoregulatory cytokine, to resistance to bloodstage malaria was investigated by infecting IL-3-deficient (knockout [KO]) mice with Plasmodium berghei NK65. Male IL-3 KO mice, but not female mice, were more resistant to infection than wild-type (WT) mice, as evidenced by lower peak parasitemia and prolonged survival. Both male and female IL-3 KO mice had increased splenomegaly and were more anemic than corresponding WT mice. Anemia was compensated for by an increase in bone marrow and splenic erythropoiesis in IL-3 KO mice, as evidenced by higher levels of erythroid progenitors. Plasma levels of gamma interferon (IFN-␥) and CXCL9 (monokine induced by IFN-␥ [MIG]) were found to be significantly reduced in IL-3 KO mice during early stages of infection. In contrast, granulocyte colony-stimulating factor (G-CSF) levels were significantly higher, and the percentage of peripheral blood neutrophils lower, in infected IL-3 KO mice than in WT counterparts. Overall, our results indicate that IL-3 plays a critical role in suppressing protective immunity to P. berghei NK65 infection and that it is involved in inhibiting the development of splenomegaly, anemia, and erythropoiesis. IL-3 also influences IFN-␥, CXCL9, and G-CSF production in response to infection. The abnormal responses seen in infected IL-3 KO mice may be due to the lack of IL-3 during development, to the lack of IL-3 in the infected mature mice, or to both.

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“…(35)(36)(37)(38)(39). Moreover, recent studies revealed a role for inflammatory monocytes, in the recruitment of CD8 + T cells to the brain of P. berghei ANKA-infected mice (40).…”

Section: Discussionmentioning

confidence: 99%

Monocyte- and Neutrophil-Derived CXCL10 Impairs Efficient Control of Blood-Stage Malaria Infection and Promotes Severe Disease

Ioannidis

Nie

et al. 2016

The Journal of Immunology

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CXCL10, or IFN-γ–inducible protein 10, is a biomarker associated with increased risk for Plasmodium falciparum–mediated cerebral malaria (CM). Consistent with this, we have previously shown that CXCL10 neutralization or genetic deletion alleviates brain intravascular inflammation and protects Plasmodium berghei ANKA-infected mice from CM. In addition to organ-specific effects, the absence of CXCL10 during infection was also found to reduce parasite biomass. To identify the cellular sources of CXCL10 responsible for these processes, we irradiated and reconstituted wild-type (WT) and CXCL10−/− mice with bone marrow from either WT or CXCL10−/− mice. Similar to CXCL10−/− mice, chimeras unable to express CXCL10 in hematopoietic-derived cells controlled infection more efficiently than WT controls. In contrast, expression of CXCL10 in knockout mice reconstituted with WT bone marrow resulted in high parasite biomass levels, higher brain parasite and leukocyte sequestration rates, and increased susceptibility to CM. Neutrophils and inflammatory monocytes were identified as the main cellular sources of CXCL10 responsible for the induction of these processes. The improved control of parasitemia observed in the absence of CXCL10-mediated trafficking was associated with a preferential accumulation of CXCR3+CD4+ T follicular helper cells in the spleen and enhanced Ab responses to infection. These results are consistent with the notion that some inflammatory responses elicited in response to malaria infection contribute to the development of high parasite densities involved in the induction of severe disease in target organs.

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Critical role of the neutrophil-associated high-affinity receptor for IgE in the pathogenesis of experimental cerebral malaria

Abstract: FcεR1-expressing neutrophils accumulate in the brain of mice infected with Plasmodium berghei (PbANKA) and promote the development of experimental cerebral malaria.

Cited by 90 publications

References 51 publications

Enhanced Basophil Reactivities during Severe Malaria and Their Relationship with the Plasmodium falciparum Histamine-Releasing Factor Translationally Controlled Tumor Protein

Enhanced Basophil Reactivities during Severe Malaria and Their Relationship with the Plasmodium falciparum Histamine-Releasing Factor Translationally Controlled Tumor Protein

Interleukin-3-Deficient Mice Have Increased Resistance to Blood-Stage Malaria

Monocyte- and Neutrophil-Derived CXCL10 Impairs Efficient Control of Blood-Stage Malaria Infection and Promotes Severe Disease

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