Phagocytosis of Plasmodium falciparum-Parasitized Erythrocytes by Human Polymorphonuclear Leukocytes

Celada, Antonio; Cruchaud, A; Perrin, Luc

doi:10.2307/3281273

Cited by 66 publications

(48 citation statements)

References 12 publications

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“…These findings are in agreement with previous studies reporting a transient increase in the activity and number of circulating phagocytes in response to schizogeny (3), and suggest that HZ could be, at least in part, responsible for such augmentation following parasite release into the bloodstream. Even though autopsy studies of P. falciparum-infected patients have yielded evidence of parasite clearance by activated M and N (43,44), neutrophilia and monocytosis occurring in malaria have also been associated with poor prognosis of the disease (45). Therefore, by inducing leukocyte recruitment into the sites of sequestration of infected RBC, -1500 g).…”

Section: Discussionmentioning

confidence: 99%

Hemozoin-Inducible Proinflammatory Events In Vivo: Potential Role in Malaria Infection

Jaramillo

Plante

Ouellet

et al. 2004

The Journal of Immunology

123

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During malaria infection, high levels of proinflammatory molecules (e.g., cytokines, chemokines) correlate with disease severity. Even if their role as activators of the host immune response has been studied, the direct contribution of hemozoin (HZ), a parasite metabolite, to such a strong induction is not fully understood. Previous in vitro studies demonstrated that both Plasmodium falciparum HZ and synthetic HZ (sHZ), β-hematin, induce macrophage/monocyte chemokine and proinflammatory cytokine secretion. In the present study, we investigated the proinflammatory properties of sHZ in vivo. To this end, increasing doses of sHZ were injected either i.v. or into an air pouch generated on the dorsum of BALB/c mice over a 24-h period. Our results showed that sHZ is a strong modulator of leukocyte recruitment and more specifically of neutrophil and monocyte populations. In addition, evaluation of chemokine and cytokine mRNA and protein expression revealed that sHZ induces the expression of chemokines, macrophage-inflammatory protein (MIP)-1α/CCL3, MIP-1β/CCL4, MIP-2/CXCL2, and monocyte chemoattractant protein-1/CCL2; chemokine receptors, CCR1, CCR2, CCR5, CXCR2, and CXCR4; cytokines, IL-1β and IL-6; and myeloid-related proteins, S100A8, S100A9, and S100A8/A9, in the air pouch exudates. Of interest, chemokine and cytokine mRNA up-regulation were also detected in the liver of i.v. sHZ-injected mice. In conclusion, our study demonstrates that sHZ is a potent proinflammatory agent in vivo, which could contribute to the immunopathology related to malaria.

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Section: Discussionmentioning

confidence: 99%

Hemozoin-Inducible Proinflammatory Events In Vivo: Potential Role in Malaria Infection

Jaramillo

Plante

Ouellet

et al. 2004

The Journal of Immunology

123

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“…36 Such cells were stained with 2Ј,7Ј-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein acetoxymethyl ester (BCECF-AM), which enabled intracellular parasites to be visualized (P.D., S. Heber, S. Baumeister, K.L., K.R., S.C.B., and S. Bhakdi, unpublished data, September 2011), and incubated with PE-labeled PMNs in the presence of active serum for 30 minutes. However, erythrophagocytosis could never be observed ( Figure 4A).…”

Section: P Falciparum Vacuoles Impair Killing Function Of Pmns 4949mentioning

confidence: 99%

Digestive vacuoles of Plasmodium falciparum are selectively phagocytosed by and impair killing function of polymorphonuclear leukocytes

Dasari

Reiß

Lingelbach

et al. 2011

Blood

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Sequestration of parasitized erythrocytes and dysregulation of the coagulation and complement system are hallmarks of severe Plasmodium falciparum malaria. A link between these events emerged through the discovery that the parasite digestive vacuole (DV), which is released together with infective merozoites into the bloodstream, dually activates the intrinsic clotting and alternative complement pathway. Complement attack occurs exclusively on the membrane of the DVs, and the question followed whether DVs might be marked for uptake by polymorphonuclear granulocytes (PMNs). We report that DVs are indeed rapidly phagocytosed by PMNs after schizont rupture in active human serum. Uptake of malaria pigment requires an intact DV membrane and does not occur when the pigment is extracted from the organelle. Merozoites are not opsonized and escape phagocytosis in nonimmune serum. Antimalarial Abs mediate some uptake of the parasites, but to an extent that is not sufficient to markedly reduce reinvasion rates. Phagocytosis of DVs induces a vigorous respiratory burst that drives the cells into IntroductionSevere malaria develops as a consequence of capillaric sequestration of parasitized RBCs (pRBCs), 1-3 activation of complement [4][5][6] and coagulation, 7-9 and increases in vascular permeability, which together can lead to microcirculatory disturbances with comatous death as the ultimate outcome. 1,7,10,11 One unresolved puzzle relates to the fact that children with severe malaria frequently suffer from septicemia due to bacteria that otherwise play no major role in this potentially fatal affliction. [12][13][14] Approximately 50% of these infections are caused by nontyphoidal Salmonellae and other Enterobacteriae, indicating a gut origin. Current hypotheses regarding the causes underlying this general state of immune compromise focus mainly on disturbances in the function of macrophages, dendritic cells, and the adaptive immune system. 15 During its developmental cycle in the RBC, the malaria parasite ingests hemoglobin and packages the waste product hemozoin, which is also known as malaria pigment, in an organelle designated the digestive vacuole (DV). 16 Copious numbers of DVs are released into the bloodstream in patients with severe Plasmodium falciparum malaria, yet their biologic properties and fates have been only minimally studied. Hematin is widely regarded to be equivalent to hemozoin, 17,18 and most investigators have focused on the effects of this artificial molecule on the immune system. [19][20][21][22][23][24][25] However, hematin is not packaged within a membrane-bound organelle and any biologic activity deriving from the DV membrane would therefore be missed. In a different study, we have shown that the DV membrane, but not hemozoin itself, is endowed with the unique capacity to dually activate the alternative complement and the intrinsic clotting pathway (P.D., S. Heber, S. Baumeister, K.L., K.R., S.C.B., and S. Bhakdi, unpublished data, September 2011). Overactivation of these ancient enzyme cascades ...

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“…There is, however, no conclusive evidence of the immune clearance of circulating gametocytes. Most in vitro studies on clearance of parasite-infected erythrocytes by phagocytosis (48,88,267,483) or by destruction via free radicals or cytokines (159,523) have focused on asexual parasites, and several studies suggest that intraerythrocytic gametocytes may not be susceptible to phagocytosis (194,425). If, on the other hand, gametocyte surface antigens can be identified and their role in gametocyte clearance can be established, these would have potential for vaccine development (459).…”

Section: Vol 24 2011mentioning

confidence: 99%

Epidemiology and Infectivity of Plasmodium falciparum and Plasmodium vivax Gametocytes in Relation to Malaria Control and Elimination

2011

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SUMMARY Malaria remains a major cause of morbidity and mortality in the tropics, with Plasmodium falciparum responsible for the majority of the disease burden and P. vivax being the geographically most widely distributed cause of malaria. Gametocytes are the sexual-stage parasites that infect Anopheles mosquitoes and mediate the onward transmission of the disease. Gametocytes are poorly studied despite this crucial role, but with a recent resurgence of interest in malaria elimination, the study of gametocytes is in vogue. This review highlights the current state of knowledge with regard to the development and longevity of P. falciparum and P. vivax gametocytes in the human host and the factors influencing their distribution within endemic populations. The evidence for immune responses, antimalarial drugs, and drug resistance influencing infectiousness to mosquitoes is reviewed. We discuss how the application of molecular techniques has led to the identification of submicroscopic gametocyte carriage and to a reassessment of the human infectious reservoir. These components are drawn together to show how control measures that aim to reduce malaria transmission, such as mass drug administration and a transmission-blocking vaccine, might better be deployed.

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Phagocytosis of Plasmodium falciparum-Parasitized Erythrocytes by Human Polymorphonuclear Leukocytes

Cited by 66 publications

References 12 publications

Hemozoin-Inducible Proinflammatory Events In Vivo: Potential Role in Malaria Infection

Hemozoin-Inducible Proinflammatory Events In Vivo: Potential Role in Malaria Infection

Digestive vacuoles of Plasmodium falciparum are selectively phagocytosed by and impair killing function of polymorphonuclear leukocytes

Epidemiology and Infectivity of Plasmodium falciparum and Plasmodium vivax Gametocytes in Relation to Malaria Control and Elimination

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