Mechanisms of immune protection in the asexual blood stage infection by Plasmodium falciparum: analysis by in vitro and ex-vivo assays

Gysin, Jürg; Druilhe, Pierre; Silva, Luiz Pereira da

doi:10.1590/s0074-02761992000900023

Cited by 8 publications

(5 citation statements)

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“…The mechanisms involved in protective immunity, either clinical or anti-parasite, remain poorly understood for vivax malaria. Antibody-dependent immune responses are considered the basic mechanism of anti-parasite immunity in P. falciparum infections (Cohen et al 1961, Fandeur et al 1984, Bouharoum-Tavoun et al 1990, Groux et al 1990, Gysin et al 1992). However, no equivalent observations are available for P. vivax and how anti-parasite immunity develops against P. vivax remains poorly understood.…”

Section: Discussionmentioning

confidence: 99%

Asymptomatic infection with Plasmodium falciparum and Plasmodium vivax in the Brazilian Amazon Basin: to treat or not to treat?

Tada¹,

Ferreira²,

Katsuragawa³

et al. 2012

Mem. Inst. Oswaldo Cruz

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Section: Discussionmentioning

confidence: 99%

Asymptomatic infection with Plasmodium falciparum and Plasmodium vivax in the Brazilian Amazon Basin: to treat or not to treat?

Tada¹,

Ferreira²,

Katsuragawa³

et al. 2012

Mem. Inst. Oswaldo Cruz

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“…Humans living in endemic areas gradually develop broad antibody repertoires to malarial antigens as they age, which is correlated with decreased severity of disease symptoms [16, 41]. This is particularly true when comparing antibody responses between uncomplicated malaria and severe malaria patients [42] as well as those comparing asymptomatic and symptomatic malaria patients.…”

Section: Discussionmentioning

confidence: 99%

“…Early experiments established that passive transfer of immune sera to naïve individuals drastically reduced symptoms of acute infection indicating that antibodies played a central role in premunition [40, 80, 81]. Later it was shown that this immunological phenomenon required cooperation between antibodies and monocytes in order to be effective [41, 82, 83]. Patient data from Malawi has recently demonstrated that in patients with severe malaria, monocytes have decreased expression of activation markers compared to those from patients with uncomplicated malaria, underscoring the role that activated monocytes play in controlling morbidity [64].…”

Section: Discussionmentioning

confidence: 99%

T cell subtypes and reciprocal inflammatory mediator expression differentiate P. falciparum memory recall responses in asymptomatic and symptomatic malaria patients in southeastern Haiti

Lehmann

Campo

Cicéron³

et al. 2017

PLoS ONE

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Asymptomatic Plasmodium falciparum infection is responsible for maintaining malarial disease within human populations in low transmission countries such as Haiti. Investigating differential host immune responses to the parasite as a potential underlying mechanism could help provide insight into this highly complex phenomenon and possibly identify asymptomatic individuals. We performed a cross-sectional analysis of individuals who were diagnosed with malaria in Sud-Est, Haiti by comparing the cellular and humoral responses of both symptomatic and asymptomatic subjects. Plasma samples were analyzed with a P. falciparum protein microarray, which demonstrated serologic reactivity to 3,877 P. falciparum proteins of known serologic reactivity; however, no antigen-antibody reactions delineating asymptomatics from symptomatics were identified. In contrast, differences in cellular responses were observed. Flow cytometric analysis of patient peripheral blood mononuclear cells co-cultured with P. falciparum infected erythrocytes demonstrated a statistically significant increase in the proportion of T regulatory cells (CD4+ CD25+ CD127-), and increases in unique populations of both NKT-like cells (CD3+ CD8+ CD56+) and CD8mid T cells in asymptomatics compared to symptomatics. Also, CD38+/HLA-DR+ expression on γδ T cells, CD8mid (CD56-) T cells, and CD8mid CD56+ NKT-like cells decreased upon exposure to infected erythrocytes in both groups. Cytometric bead analysis of the co-culture supernatants demonstrated an upregulation of monocyte-activating chemokines/cytokines in asymptomatics, while immunomodulatory soluble factors were elevated in symptomatics. Principal component analysis of these expression values revealed a distinct clustering of individual responses within their respective phenotypic groups. This is the first comprehensive investigation of immune responses to P. falciparum in Haiti, and describes unique cell-mediated immune repertoires that delineate individuals into asymptomatic and symptomatic phenotypes. Future investigations using large scale biological data sets analyzing multiple components of adaptive immunity, could collectively define which cellular responses and molecular correlates of disease outcome are malaria region specific, and which are truly generalizable features of asymptomatic Plasmodium immunity, a research goal of critical priority.

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“…Purified human hyperimmune gamma globulins prepared from West African hyperimmune adults and protective in passive transfer assays in humans (HIG 1 ) (25) were kindly provided by P. Druilhe. These Igs were also efficient at clearing infections of Saimiri monkeys with the FUP/SP-O parasites (12). The activity on R parasites has not been tested in passive transfer assays.…”

Section: Methodsmentioning

confidence: 99%

Novel Target Antigens of the Variant-Specific Immune Response toPlasmodium falciparumIdentified by Differential Screening of an Expression Library

et al. 1999

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A primary infection by the Plasmodium falciparum Palo Alto O and R antigenic variants induces a variantspecific immunity in the Saimiri sciureus monkey. We have shown that these variants express distinct PfEMP1 antigens and differ in their levels of expression of additional antigens, including two conserved erythrocyte membrane-associated proteins, HRP1 and PfEMP3. To identify the antigens eliciting a variant-specific response, we conducted a differential screening of a gt11 library with variant-specific sera. We report here the analysis of the 46 anti-R-specific clones. Two specific targets of the anti-R response were identified: (i) PfEMP3, suggesting that immunogenicity of this antigen is modulated by its relative abundance in different variants, and (ii) Asn-rich motifs. Most anti-R-specific clones, derived from so-far-undescribed genes, were detected by a cross-reaction on poly(Asn) stretches, as indicated by elimination of the signal after absorption on Asn-rich sequences. Reverse transcription-PCR (RT-PCR) showed that expression of the gene defined by clone 13 was R specific. Pepscan analysis of clone 13 identified three Asn-rich polypeptides and one unique peptide reacting specifically with antibodies eluted from the R-infected erythrocyte surface. Antisera raised to the unique peptide reacted with an R-specific protein. Attempts to demonstrate that clone 13 was derived from a var gene by using PCRs combining clone 13 and var-derived primers were unsuccessful. The var genes expressed by O and R parasites were identified not by this strategy but by RT-PCR with var-specific primers. This work has provided novel insights into immunity to antigenic variants and has identified a novel gene switched on during antigenic variation.

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Mechanisms of immune protection in the asexual blood stage infection by Plasmodium falciparum: analysis by in vitro and ex-vivo assays

Cited by 8 publications

References 0 publications

Asymptomatic infection with Plasmodium falciparum and Plasmodium vivax in the Brazilian Amazon Basin: to treat or not to treat?

Asymptomatic infection with Plasmodium falciparum and Plasmodium vivax in the Brazilian Amazon Basin: to treat or not to treat?

T cell subtypes and reciprocal inflammatory mediator expression differentiate P. falciparum memory recall responses in asymptomatic and symptomatic malaria patients in southeastern Haiti

Novel Target Antigens of the Variant-Specific Immune Response toPlasmodium falciparumIdentified by Differential Screening of an Expression Library

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