Involvement of Inflammatory Chemokines in Survival of Human Monocytes Fed with Malarial Pigment

Giribaldi, Giuliana; Prato, Maurizio; Ulliers, Daniela; Gallo, Valentina; Schwarzer, Evelin; Akide-Ndunge, Oskar B.; Valente, Elena; Saviozzi, Silvia; Calogero, Raffaele; Arese, Paolo

doi:10.1128/iai.00455-10

Cited by 53 publications

(60 citation statements)

References 68 publications

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“…It is all the more remarkable that, whereas seminal work on the biogenesis and biochemical events occurring within the DV is ongoing, 34,35,[41][42][43] only one group of investigators has been conducting studies with naturally released DVs, and these are devoted to their effects on monocyte functions. [44][45][46][47][48] The first study was conducted with unpurified malarial pigment obtained by hypotonic lysis of infected erythrocytes. In that study, evidence was presented that the pigment was phagocytosed by human macrophages, and that this provoked a respiratory burst that was blunted upon subsequent provocation.…”

Section: Discussionmentioning

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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Section: Discussionmentioning

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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“…6,8,19 Inhibitory effects, such as inhibition of erythropoiesis, 7 dendritic cell maturation, 19 antigen presentation, 6 and abrogation of the ability to kill ingested bacteria 3 and to repeat phagocytic cycles, 8 are long-term effects that typically start 4-6 hours after completion of phagocytosis and may persist during several days. 7,16,18 Short-term stimulatory effects 5,8 elicited by yet undisclosed mechanisms were occasionally described but have received little attention so far.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, results obtained here with nHZ or RBs will be preferentially considered and discussed. nHZ has been shown to induce both stimulatory 3,5,18 and inhibitory effects in HZ-laden human monocytes. 6,8,19 Inhibitory effects, such as inhibition of erythropoiesis, 7 dendritic cell maturation, 19 antigen presentation, 6 and abrogation of the ability to kill ingested bacteria 3 and to repeat phagocytic cycles, 8 are long-term effects that typically start 4-6 hours after completion of phagocytosis and may persist during several days.…”

Section: Discussionmentioning

confidence: 99%

Host fibrinogen stably bound to hemozoin rapidly activates monocytes via TLR-4 and CD11b/CD18-integrin: a new paradigm of hemozoin action

Barrera

Skorokhod

Baci

et al. 2011

Blood

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Natural hemozoin (nHZ), prepared after schizogony, consists of crystalline ferriprotoporphyrin-IX dimers from undigested heme bound to host and parasite proteins and lipids. Phagocytosed nHZ alters important functions of host phagocytes. Most alterations are long-term effects. We show that host fibrinogen (FG) was constantly present (at ϳ 1 FG per 25 000 HZ-heme molecules) and stably bound to nHZ from plasma-cultured parasites. FG was responsible for the rapid 100-fold stimulation of reactive oxygen species production and 50-fold increase of TNF and monocyte chemotactic protein 1 by human monocytes. Those effects, starting within minutes after nHZ cell contact, were because of interaction of FG with FG-receptors TLR4 and integrin CD11b/CD18. Receptor blockage by specific mAbs or removal of FG from nHZ abrogated the effects. nHZ-opsonizing IgGs contribute to the stimulatory response but are not essential for FG effects. Immediate increase in reactive oxygen species and TNF may switch on previously described long-term effects of nHZ, largely because of HZ-generated lipo-peroxidation products 15(S,R)-hydroxy-6,8,11,13-eicosatetraenoic acid and 4-hydroxynonenal. The FG/HZ effects mediated by TLR4/integrins represent a novel paradigm of nHZ activity and allow expansion of nHZ effects to nonphagocytic cells, such as endothelia and airway epithelia, and lead to a better understanding of organ pathology in malaria. (Blood. 2011;117(21):5674-5682) IntroductionNatural hemozoin (nHZ), as present in the food vacuole of Plasmodium falciparum and largely coincident with residual bodies (RBs) shed during schizogony, consists of a scaffold of crystalline ferriprotoporphyrin IX dimers (␤-hematin, BH) from undigested host hemoglobin-heme 1 bound to a vast array of host and parasite molecules. [2][3][4] nHZ is phagocytosed in vivo and in vitro by host phagocytes and alters important functions in those cells. Most functional alterations were long-term postphagocytic effects. 3,[5][6][7][8] Some of those long-term effects were also reported in human and murine phagocytes fed with BH or variously manipulated HZ. 9,10 By contrast, a powerful, short-term stimulation of oxidative burst by human monocytes was also shown to occur during phagocytosis of nHZ. 8 Here, we show that host fibrinogen (FG) was constantly present and stably bound to nHZ and RBs prepared from parasites cultured in presence of plasma. FG in nHZ was responsible for a prephagocytic rapid and powerful stimulation of oxidative burst, accompanied by release of TNF and monocyte chemotactic protein 1 (MCP-1) by human monocytes. Those prephagocytic events were because of the interaction of FG with TLR4 and integrin CD11b/CD18 (CR3, Mac-1), known receptors for FG as an immune-active molecule. [11][12][13] Present data are the first indication that nHZ-bound FG may act as a powerful self-signal molecule for early immune responses and a trigger for the persistent long-term effects that play multiple roles in malaria pathogenesis. Methods ReagentsUnless otherwise stated, reagen...

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“…After hemozoin-phagocytosis, serious dysfunctions of monocytes have been reported, including repeated phagocytosis [12] , bacterial killing abilities [13] , oxidative bursts [14] , MHC class II expression and antigen presentation [13] , maturation to dendritic cells [15] , and coordination of erythropoiesis [16] . In [17] . Experimental data from hemozoinfed monocytes demonstrated that hemozoin can induce extensive degradation of IκBα.…”

Section: Effect Of Hemozoin On Blood Mononuclear Cellsmentioning

confidence: 99%

Effect of malaria components on blood mononuclear cells involved in immune response

Punsawad

2013

Asian Pacific Journal of Tropical Biomedicine

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Involvement of Inflammatory Chemokines in Survival of Human Monocytes Fed with Malarial Pigment

Cited by 53 publications

References 68 publications

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

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

Host fibrinogen stably bound to hemozoin rapidly activates monocytes via TLR-4 and CD11b/CD18-integrin: a new paradigm of hemozoin action

Effect of malaria components on blood mononuclear cells involved in immune response

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