Cryoglobulins, circulating immune complexes, and complement activation in cerebral malaria

Adam, C; Géniteau, M; Gougerot‐Pocidalo, Marie‐Anne; Verroust, P; Lebras, J.; Gibert, Christelle; Morel-Marogér, L

doi:10.1128/iai.31.2.530-535.1981

Cited by 70 publications

(25 citation statements)

References 23 publications

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“…For example, it was shown that the parasite digestive vacuole, which during schizont rupture is released together with the MZs into the blood stream, activates the ACP (Dasari et al, 2012(Dasari et al, , 2014. Malaria infection-induced complement activation of the classical pathway via the formation of antigen-antibody immune complexes as well as activation of the mannose-binding lectin pathway have also been reported (Jhaveri et al, 1997;Adam et al, 1981;Klabunde et al, 2002;Garred et al, 2003;Stoute et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

ThePlasmodium falciparumblood stages acquire factor H family proteins to evade destruction by human complement

Rosa

Flammersfeld

Ngwa

et al. 2015

Cellular Microbiology

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SummaryThe acquisition of regulatory proteins is a means of blood‐borne pathogens to avoid destruction by the human complement. We recently showed that the gametes of the human malaria parasite Plasmodium falciparum bind factor H (FH) from the blood meal of the mosquito vector to assure successful sexual reproduction, which takes places in the mosquito midgut. While these findings provided a first glimpse of a complex mechanism used by Plasmodium to control the host immune attack, it is hitherto not known, how the pathogenic blood stages of the malaria parasite evade destruction by the human complement. We now show that the human complement system represents a severe threat for the replicating blood stages, particularly for the reinvading merozoites, with complement factor C3b accumulating on the surfaces of the intraerythrocytic schizonts as well as of free merozoites. C3b accumulation initiates terminal complement complex formation, in consequence resulting in blood stage lysis. To inactivate C3b, the parasites bind FH as well as related proteins FHL‐1 and CFHR‐1 to their surface, and FH binding is trypsin‐resistant. Schizonts acquire FH via two contact sites, which involve CCP modules 5 and 20. Blockage of FH‐mediated protection via anti‐FH antibodies results in significantly impaired blood stage replication, pointing to the plasmodial complement evasion machinery as a promising malaria vaccine target.

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Section: Introductionmentioning

confidence: 99%

ThePlasmodium falciparumblood stages acquire factor H family proteins to evade destruction by human complement

Rosa

Flammersfeld

Ngwa

et al. 2015

Cellular Microbiology

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“…Also, by cross‐linking Fc receptors on effector cells such as macrophages and monocytes, ICs can stimulate the production of pro‐inflammatory cytokines (16) that have been proposed to have a role in the pathogenesis of severe malaria (17). Despite the accumulating evidence linking ICs to the pathogenesis of malaria (2,5,6,18–20), no clear pattern of association between antibody class or subclass and the clinical form of severe malaria has emerged. Therefore, the main objective of this study was to determine the composition of ICs in terms of antibody class/subclass and to relate this to the severity of P. falciparum malaria.…”

Section: Discussionmentioning

confidence: 99%

“…ICs can activate complement and deposit in tissues stimulating an inflammatory response (4). Therefore, some investigators have suggested a possible role for ICs in the pathogenesis of SMA and CM (5,6).…”

Section: Introductionmentioning

confidence: 99%

Distinct pattern of class and subclass antibodies in immune complexes of children with cerebral malaria and severe malarial anaemia

Mibei

Otieno

Orago

et al. 2008

Parasite Immunology

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SUMMARY Plasmodium falciparum infection can lead to deadly complications such as severe malaria‐associated anaemia (SMA) and cerebral malaria (CM). Children with severe malaria have elevated levels of circulating immune complexes (ICs). To further investigate the quantitative differences in antibody class/subclass components of ICs in SMA and CM, we enrolled 75 children with SMA and 32 children with CM from hospitals in western Kenya and matched them to 74 and 52 control children, respectively, with uncomplicated symptomatic malaria. Total IgG IC levels were always elevated in children with malaria upon enrolment, but children with CM had the highest levels of any group. Conditional logistic regression showed a borderline association between IgG4‐containing IC levels and increased risk of SMA (OR = 3·11, 95% CI 1·01–9·56, P = 0·05). Total IgG ICs (OR = 2·84, 95% CI 1·08–7·46, P = 0·03) and IgE‐containing ICs (OR = 6·82, OR 1·88–24·73, P ≤ 0·01) were associated with increased risk of CM. These results point to differences in the contribution of the different antibody class and subclass components of ICs to the pathogenesis of SMA and CM and give insight into potential mechanisms of disease.

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“…A possible explanation for platelet activation in malaria is complement formation. The formation of C3d, indicating complement activation, was associated with thrombocytopenia in malaria-infected patients [101]. Nevertheless activation of platelets in malaria could also be related to direct interaction with the parasites [102,103].…”

Section: Malariamentioning

confidence: 99%

Platelet interactions with viruses and parasites

Alonso

Cox

2015

Platelets

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Cryoglobulins, circulating immune complexes, and complement activation in cerebral malaria

Cited by 70 publications

References 23 publications

ThePlasmodium falciparumblood stages acquire factor H family proteins to evade destruction by human complement

ThePlasmodium falciparumblood stages acquire factor H family proteins to evade destruction by human complement

Distinct pattern of class and subclass antibodies in immune complexes of children with cerebral malaria and severe malarial anaemia

Platelet interactions with viruses and parasites

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