Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity

Stone, Will; Campo, Joseph J.; Ouédraogo, André Lin; Meerstein-Kessel, Lisette; Morlais, Isabelle; Da, Dari; Cohuet, Anna; Nsango, Sandrine E.; Sutherland, Colin J.; Vegte‐Bolmer, Marga van de; Siebelink-Stoter, Rianne; Gemert, Geert Jan van; Graumans, Wouter; Lanke, Kjerstin; Shandling, Adam D.; Pablo, Jozelyn; Teng, Andy; Jones, Sophie; Jong, Roos M. de; Fabra-García, Amanda; Bradley, John; Roeffen, Will; Lasonder, Edwin; Gremo, Giuliana; Schwarzer, Evelin; Janse, Chris J.; Singh, Susheel K.; Theisen, Michael; Felgner, Phil; Marti, Matthias; Drakeley, Chris; Sauerwein, Robert W.; Bousema, Teun; Jore, Matthijs M.

doi:10.1038/s41467-017-02646-2

Cited by 87 publications

(108 citation statements)

References 76 publications

Supporting

Mentioning

106

Contrasting

Order By: Relevance

“…As an illustration of the utility of gametocyte-specific proteins as markers of gametocyte exposure, we utilized protein microarray data from a study that aimed to characterize the immune profile associated with transmission-reducing immunity in naturally infected gametocyte carriers (Stone, Campo et al 2017 accepted manuscript 36 ). For the current study, we compared responses to our gold standard gametocyte genes (n=40) and novel gametocyte genes from our 100 highest scoring proteins that were on the array (n=30).…”

Section: Resultsmentioning

confidence: 99%

“…As an alternative approach to the detection of gametocyte carriage in populations, we utilized a gametocyte-enriched protein microarray (Stone, Campo et al . 2017 accepted manuscript 36 ) to determine antibody responses to genes that we here describe as highly gametocyte-specific. The bacterial expression system used for the array has known limitations with the expression of conformational proteins 52 and should thus be considered a ‘rule in’ rather than ‘rule out’ approach to immune recognition.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Probabilistic data integration identifies reliable gametocyte-specific proteins and transcripts in malaria parasites

Meerstein-Kessel

Lee

Lanke

et al. 2017

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Probabilistic data integration identifies reliable gametocyte-specific proteins and transcripts in malaria parasites

Meerstein-Kessel

Lee

Lanke

et al. 2017

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

“…We first postulated that the natural blocking immunity of the human host could play a role. To test this possibility, the natural serum of isolates K to P was replaced by naive AB serum (Gouagna et al , 2004; Da et al , 2015; Stone et al , 2018) (Additional file 1). Similar to assays using unchanged natural serum (isolates A to J), assays with serum replacement showed either increased (L, N, O, and P) or decreased (K and M) infection in irradiated mosquitoes (Additional file 1: Figure S2).…”

Section: Discussionmentioning

confidence: 99%

“…Gametocyte carrier blood was collected by venipuncture into heparinized tubes. To test for a possible interaction between the natural blocking immunity of the human host (Gouagna et al ., 2004; Da et al ., 2015; Stone et al ., 2018) and the irradiation on mosquito infection, DMFA were performed using either whole donor blood or with replacement of the serum by a non-immune AB serum (see Additional file 1). Mosquitoes were starved of glucose solution for 12 h prior to the exposure.…”

Section: Methodsmentioning

confidence: 99%

Effect of irradiation on the survival and susceptibility of femaleAnopheles arabiensisto natural isolates ofPlasmodium falciparum

Guissou

Poda

Hien

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

25Background: The sterile insect technique (SIT) is a vector control strategy relying on the mass 26 release of sterile males into wild vector populations. Current sex separation techniques are not 27 fully efficient and could lead to the release of a small proportion of females. It is therefore 28 important to evaluate the effect of irradiation on the ability of released females to transmit 29 pathogens. This study aimed to assess the effect of irradiation on the survival and competence 30 of Anopheles arabiensis females for Plasmodium falciparum in laboratory conditions. 31Methods: Pupae were irradiated at 95 Gy, a sterilizing dose of gamma-rays from Caesium-137 32 source, and emerging adult females were challenged with one of 14 natural isolates of P. 33 falciparum. Seven days post-bloodmeal (dpbm), irradiated and unirradiated-control females 34 were dissected to assess the presence of oocysts. On 14 dpbm, oocyst rupture in mosquito 35 midguts and sporozoite dissemination in head/thoraces were also examined. Two assays were 36 performed to gauge the effect of irradiation on An. arabiensis survival. First, the survivorship 37 of irradiated and unirradiated-control mosquitoes exposed to each parasite isolate was 38 monitored. Second, how parasite infection and irradiation interact to influence mosquito 39 lifespan was also assessed by including a group of uninfected unirradiated mosquitoes. 40Results: Overall, irradiation reduced the proportion of infected mosquitoes but this effect was 41 inconsistent among parasite isolates. Second, there was no significant effect of irradiation on 42 the number of developing oocysts. Third, the proportion of ruptured oocysts at 14 dpbm was 43 higher in irradiated-than in control-unirradiated females, suggesting that irradiation might 44 speed up parasite development. Fourth, irradiation had varying effects on female survival with 45 either a negative effect (assay 1) or no effect (assay 2). 46 Conclusion: Combining these effects into an epidemiological model could help quantifying the 47 net effect of irradiation on malaria transmission in this system. Together, our data indicate that 48 irradiated female An. arabiensis could contribute to malaria transmission, and highlight the 49 need for perfect sexing tools which would prevent the release of females as part of SIT 50 programs.51 52 Key words: Sterile Insect Technique (SIT), competence, Direct membrane feeding assay 53 54 55 56 57 58The worldwide annual incidence of malaria declined by 36 % between 2000 and 2015 59 (Cibulskis et al., 2016). Control measures based on vector management have played an 60 important role in reducing malaria transmission with, for example, the use of long-lasting 61 insecticide-treated nets contributing to an estimated 68 % of the decline in Plasmodium 62 falciparum incidence over this period (Bhatt et al., 2015). Since 2015 however, global progress 63 has stalled, and several African countries are currently experiencing an increase in malaria 64 incidence (WHO, 2018). The reasons for these r...

show abstract

“…Total DNA and total RNA were isolated from subjects’ dried blood spots at V1 using nucleic acid purification kits (Norgen Biotek #35300, #36000), and cDNAs were used in qRT-PCR assays [20, 21]. These cDNAs were used to measure RNA expression levels of P. falciparum gametocyte-specific genes, including Pfs25 (mature gametocyte), Pfs16 (early gametocyte) [22], and Pfs230 , which encodes a gametocyte antigen important for eliciting host antibodies that inhibit parasite transmission to a mosquito host [23, 24].…”

Section: Methodsmentioning

confidence: 99%

Signatures of divergent antimalarial treatment responses in peripheral blood from infants and adults in Malawi

Maurizio

Fuseini

Tegha

et al. 2019

Preprint

View full text Add to dashboard Cite

Background: Heterogeneity in the immune response to parasite infection is mediated in part by differences in host genetics, sex, and age group. In neonates and infants, ongoing immunological maturation often results in increased susceptibility to infection and variable responses to drug treatment, increasing the risk of complications. Even though significant age-specific effects on host cytokine responses to Plasmodium falciparum infection have been identified, age effects on uncomplicated malaria infection and antimalarial treatment remain poorly understood.Methods: In samples of whole blood from a cohort of naturally infected malaria-positive individuals in Malawi (n=63 total; 34 infants <2 years old, 29 adults >18 years old), we assessed blood cytokine levels and characterized monocyte and dendritic cell frequencies at two timepoints: acute infection, and four weeks post antimalarial treatment. We modeled the effects of age group, sex, and timepoint, and evaluated the role of these factors on infection and treatment outcomes.Results: Regardless of treatment timepoint, in our population age was significantly associated with overall blood hemoglobin, which was higher in adults, and plasma nitric oxide, IL-10, and TNF-α levels, which were higher in infants. We found a significant effect of age on the hemoglobin treatment response, whereby after treatment, levels increased in infants and decreased in adults. Furthermore, we observed significant age-specific effects on treatment response for overall parasite load, IFN-γ, and IL-12(p40), and these effects were sex-dependent. We uncovered significant age effects on the overall levels and treatment response of myeloid dendritic cell frequencies. In addition, within each age group, we found continuous age effects on gametocyte levels (Pfs16 ), TNF-α, and nitric oxide. Conclusions:In a clinical study of infants and adults experiencing natural malaria infection and receiving antimalarial treatment, we identified age-specific signatures of infection and treatment responses in peripheral blood. We describe host markers that may indicate, and potentially mediate, differential post-treatment outcomes for malaria in infants versus adults.

show abstract

Unravelling the immune signature of Plasmodium falciparum transmission-reducing immunity

Cited by 87 publications

References 76 publications

Probabilistic data integration identifies reliable gametocyte-specific proteins and transcripts in malaria parasites

Probabilistic data integration identifies reliable gametocyte-specific proteins and transcripts in malaria parasites

Effect of irradiation on the survival and susceptibility of femaleAnopheles arabiensisto natural isolates ofPlasmodium falciparum

Signatures of divergent antimalarial treatment responses in peripheral blood from infants and adults in Malawi

Contact Info

Product

Resources

About