scholarly journals Malian adults maintain serologic responses to virulent PfEMP1s amid seasonal patterns of fluctuation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Noah T. Ventimiglia ◽  
Emily M. Stucke ◽  
Drissa Coulibaly ◽  
Andrea A. Berry ◽  
Kirsten E. Lyke ◽  
...  

AbstractPlasmodium falciparum erythrocyte membrane protein-1s (PfEMP1s), diverse malaria proteins expressed on the infected erythrocyte surface, play an important role in pathogenesis, mediating adhesion to host vascular endothelium. Antibodies to particular non-CD36-binding PfEMP1s are associated with protection against severe disease. We hypothesized that given lifelong P. falciparum exposure, Malian adults would have broad PfEMP1 serorecognition and high seroreactivity levels during follow-up, particularly to non-CD36-binding PfEMP1s such as those that attach to endothelial protein C receptor (EPCR) and intercellular adhesion molecule-1 (ICAM-1). Using a protein microarray, we determined serologic responses to 166 reference PfEMP1 fragments during a dry and subsequent malaria transmission season in Malian adults. Malian adult sera had PfEMP1 serologic responses throughout the year, with decreased reactivity to a small subset of PfEMP1 fragments during the dry season and increases in reactivity to a different subset of PfEMP1 fragments during the subsequent peak malaria transmission season, especially for intracellular PfEMP1 domains. For some individuals, PfEMP1 serologic responses increased after the dry season, suggesting antigenic switching during asymptomatic infection. Adults were more likely to experience variable serorecognition of CD36-binding PfEMP1s than non-CD36-binding PfEMP1s that bind EPCR or ICAM-1, which remained serorecognized throughout the year. Sustained seroreactivity to non-CD36-binding PfEMP1s throughout adulthood amid seasonal fluctuation patterns may reflect underlying protective severe malaria immunity and merits further investigation.

mBio ◽  
2016 ◽  
Vol 7 (4) ◽  
Author(s):  
Marion Avril ◽  
Maria Bernabeu ◽  
Maxwell Benjamin ◽  
Andrew Jay Brazier ◽  
Joseph D. Smith

ABSTRACT Intercellular adhesion molecule 1 (ICAM-1) and the endothelial protein C receptor (EPCR) are candidate receptors for the deadly complication cerebral malaria. However, it remains unclear if Plasmodium falciparum parasites with dual binding specificity are involved in cytoadhesion or different parasite subpopulations bind in brain microvessels. Here, we investigated this issue by studying different subtypes of ICAM-1-binding parasite lines. We show that two parasite lines expressing domain cassette 13 (DC13) of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) family have dual binding specificity for EPCR and ICAM-1 and further mapped ICAM-1 binding to the first DBLβ domain following the PfEMP1 head structure in both proteins. As PfEMP1 head structures have diverged between group A (EPCR binders) and groups B and C (CD36 binders), we also investigated how ICAM-1-binding parasites with different coreceptor binding traits influence P. falciparum -infected erythrocyte binding to endothelial cells. Whereas levels of binding to tumor necrosis factor alpha (TNF-α)-stimulated endothelial cells from the lung and brain by all ICAM-1-binding parasite lines increased, group A (EPCR and ICAM-1) was less dependent than group B (CD36 and ICAM-1) on ICAM-1 upregulation. Furthermore, both group A DC13 parasite lines had higher binding levels to brain endothelial cells (a microvascular niche with limited CD36 expression). This study shows that ICAM-1 is a coreceptor for a subset of EPCR-binding parasites and provides the first evidence of how EPCR and ICAM-1 interact to mediate parasite binding to both resting and TNF-α-activated primary brain and lung endothelial cells. IMPORTANCE Cerebral malaria is a severe neurological complication of P. falciparum infection associated with infected erythrocyte (IE) binding in cerebral vessels. Yet little is known about the mechanisms by which parasites adhere in the brain or other microvascular sites. Here, we studied parasite lines expressing group A DC13-containing PfEMP1 variants, a subset that has previously been shown to have high brain cell- and other endothelial cell-binding activities. We show that DC13-containing PfEMP1 variants have dual EPCR- and ICAM-1-binding activities and that both receptors are involved in parasite adherence to lung and brain endothelial cells. As both EPCR and ICAM-1 are implicated in cerebral malaria, these findings suggest the possibility that parasites with dual binding activities are involved in parasite sequestration to microvascular beds with low CD36 expression, such as the brain, and we urge more research into the multiadhesive properties of PfEMP1 variants.


1999 ◽  
Vol 67 (2) ◽  
pp. 972-975 ◽  
Author(s):  
Jeffery A. Hobden ◽  
Sharon Masinick-McClellan ◽  
Ronald P. Barrett ◽  
Kenneth S. Bark ◽  
Linda D. Hazlett

ABSTRACT In this study, the role of intercellular adhesion molecule 1 (ICAM-1) in the pathogenesis of Pseudomonas aeruginosakeratitis was examined by using inbred ICAM-1-deficient knockout mice. These mice had significantly less (P ≤ 0.02) ocular disease than wild-type mice, suggesting that ICAM-1 contributes to a more severe disease response following P. aeruginosainfection.


2019 ◽  
Author(s):  
Lin Yang ◽  
Ruilian Xin ◽  
Shanchun Guo ◽  
Mingli Liu

Abstract BACKGROUND : During P. falciparum infection, the binding of P. falciparum erythrocyte membrane protein 1 (PfEMP1) to endothelial cells (EC) results in the sequestration of pRBC. Several receptors located on the endothelial cells, including intercellular adhesion molecule 1 (ICAM-1), CD36, and endothelial protein C receptor (EPCR), contribute to PfEMP1 adhesion to the microvasculature. PfEMP1, expressed on the surface of parasitized red blood cells (pRBC), is composed of cysteine-rich interdomain regions (CIDR) and Duffy binding-like (DBL) domains. CIDRα1 competitively binds to EPCR with activated protein C (APC) and impairs cytoprotective and anticoagulant effects by APC, which plays important roles in severe malaria (SM) pathogenesis such as cerebral malaria (CM) and severe malaria anemia (SMA). The strategy to inhibit EPCR binding to pRBC while concomitantly strengthen its binding to APC may be crucial in restoring disrupted protein C (PC) system’s function. The purpose of this study is to evaluate the association between malaria severity and the EPCR genotypes as well as with soluble EPCR (sEPCR), and the study also addresses the physiological relevance of EPCR genetic polymorphism. RESULTS : In this study, we conducted a meta-analysis on the eligible studies by comparing the frequency of EPCR rs867186-GG versus rs867186-GA and -AA genotype in SM, mild malaria (MM) or uncomplicated malaria (UM) patients and healthy individuals from Thailand, Uganda, Benin, Tanzania, and Ghana. We also determined the relationship between rs867186 genotype and sEPCR levels. Our results showed that the genotype rs867186-GG is higher in MM/UM than in SM patients. SM patients carrying the rs867186-GG genotype have higher plasma soluble EPCR (sEPCR) levels than in rs867186-AG and rs867186-AA carriers. MM/UM patients carrying the rs867186-AG genotype have significantly higher level of sEPCR compared to those carrying rs867186-AA. Similarly, the rs867186-GG is associated with high sEPCR level in healthy individuals. CONCLUSIONS : This meta-analysis demonstrates that pRBCs and EPCR interactions are associated with malaria severity, and treatments that block their binding via PfEMP1 CIDRα1 could be a potential therapy for SM.


1990 ◽  
Vol 25 (1-3) ◽  
pp. 237-242 ◽  
Author(s):  
Thor G. Theander ◽  
Lars Hviid ◽  
Yousif A. Abu-Zeid ◽  
NasrEldin H. Abdulhadi ◽  
Bakri O. Saeed ◽  
...  

2012 ◽  
Vol 39 (3) ◽  
pp. 510-515 ◽  
Author(s):  
PETER M. IZMIRLY ◽  
MARIANNA SHVARTSBEYN ◽  
SHANE MEEHAN ◽  
ANDREW FRANKS ◽  
ALAN BRAUN ◽  
...  

Objective.Membrane endothelial protein C receptor (mEPCR) is highly expressed in peritubular capillaries of kidneys from patients with active and poorly responsive lupus nephritis (LN). We investigated the hypothesis that changes in the microvasculature are widespread with extension to the dermal vasculature.Methods.Skin biopsies from uninvolved skin (buttocks) were performed in 27 patients with LN and 5 healthy controls. Sections were stained with specific antibodies reactive with mEPCR, adiponectin, intercellular adhesion molecule-1 (ICAM-1), and CD31; then assessed by enumeration of stained blood vessels (percentage positive blood vessels) blinded to knowledge of clinical information.Results.There was a significant increase in the prevalence of blood vessels that stained for mEPCR and ICAM-1 in patients compared to controls [94% vs 59% (p = 0.045) and 81% vs 67% (p = 0.037), respectively]. Adiponectin staining and CD31 staining were similar between the groups (45% vs 43% and 98% vs 92%). Dermal staining for mEPCR was greater in patients with proliferative glomerulonephritis than in those with membranous disease (96% vs 60%; p = 0.029). A composite of poor prognostic renal markers and death was significantly associated with greater expression of mEPCR staining.Conclusion.These data are consistent with the notion that in patients with LN, activation of the microvasculature extends beyond the clinically targeted organ. The insidious expression of this widespread vasculopathy may be a contributor to longterm comorbidities.


Author(s):  
Ludwig Traby ◽  
Marietta Kollars ◽  
Manuel Kussmann ◽  
Matthias Karer ◽  
Hana Sinkovec ◽  
...  

Objectives Pulmonary thrombus formation is a hallmark of coronavirus disease 2019 (COVID-19). A dysregulated immune response culminating in thromboinflammation has been described, but the pathomechanisms remain unclear. Methods We studied 41 adult COVID-19 patients with positive results on reverse-transcriptase polymerase-chain-reaction assays and 37 sex-and age-matched healthy controls. Number and surface characteristics of extracellular vesicles (EV) and citrullinated histone H 3 levels were determined in plasma upon inclusion by flowcytometry and immunoassay. Results 20 patients had severe and 21 non-severe disease. The number of EV [median, (25th, 75th percentile)] was significantly higher in patients compared with controls [658.8 (353.2, 876.6) vs 435.5 (332.5, 585.3), geometric mean ratio (95% confidence intervals): 2.6 (1.9, 3.6); p<0.001]. Patients exhibited significantly higher numbers of EV derived from platelets, endothelial cells, leukocytes, or neutrophils than controls. EV from alveolar-macrophages and alveolar-epithelial-cells were detectable in plasma and were significantly higher in patients. Intercellular Adhesion Molecule 1-positive EV levels were higher in patients, while no difference between tissue factor-positive and angiotensin converting enzyme-positive EV was seen between both groups. Levels of EV did not differ between patients with severe and non-severe COVID-19. Citrullinated histone H 3 levels [ng/ml, median (25th, 75th percentile)] were higher in patients than in controls [1.42 (0.6, 3.4) vs 0.31 (0.1, 0.6), geometric mean ratio: 4.44 (2.6, 7.7); p<0.001], and were significantly lower in patients with non-severe disease compared to those with severe disease. Conclusion EV and citrullinated histone H 3 are associated with COVID-19 and could provide information regarding pathophysiology of the disease.


2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Protus Omondi ◽  
Marion Burugu ◽  
Damaris Matoke-Muhia ◽  
Edwin Too ◽  
Eva A. Nambati ◽  
...  

Abstract Background The efficacy and safety of artemether–lumefantrine (AL) and dihydroartemisinin–piperaquine (DP) against asexual parasites population has been documented. However, the effect of these anti-malarials on sexual parasites is still less clear. Gametocyte clearance following treatment is essential for malaria control and elimination efforts; therefore, the study sought to determine trends in gametocyte clearance after AL or DP treatment in children from a malaria-endemic site in Kenya. Methods Children aged between 0.5 and 12 years from Busia, western Kenya with uncomplicated Plasmodium falciparum malaria were assigned randomly to AL or DP treatment. A total of 334 children were enrolled, and dried blood spot samples were collected for up to 6 weeks after treatment during the peak malaria transmission season in 2016 and preserved. Plasmodium falciparum gametocytes were detected by qRT-PCR and gametocyte prevalence, density and mean duration of gametocyte carriage were determined. Results At baseline, all the 334 children had positive asexual parasites by microscopy, 12% (40/334) had detectable gametocyte by microscopy, and 83.7% (253/302) children had gametocytes by RT-qPCR. Gametocyte prevalence by RT-qPCR decreased from 85.1% (126/148) at day 0 to 7.04% (5/71) at day 42 in AL group and from 82.4% (127/154) at day 0 to 14.5% (11/74) at day 42 in DP group. The average duration of gametocyte carriage as estimated by qRT-PCR was slightly shorter in the AL group (4.5 days) than in the DP group (5.1 days) but not significantly different (p = 0.301). Conclusion The study identifies no significant difference between AL and DP in gametocyte clearance. Gametocytes persisted up to 42 days post treatment in minority of individuals in both treatment arms. A gametocytocidal drug, in combination with artemisinin-based combination therapy, will be useful in blocking malaria transmission more efficiently.


2019 ◽  
Author(s):  
Jessy Goupeyou-Youmsi ◽  
Tsiriniaina Rakotondranaivo ◽  
Nicolas Puchot ◽  
Ingrid Peterson ◽  
Romain Girod ◽  
...  

AbstractBackgroundMalaria is still a heavy public health concern in Madagascar. Few studies combining parasitology and entomology have been recently conducted despite the need for such information to design proper vector control measures. In a region of moderate to intense transmission of both Plasmodium falciparum and Plasmodium vivax, we conducted a combined parasitology and entomology survey in two nearby villages, across a malaria transmission season from December 2016 to April 2017.Methodology/Principal findingsCommunity-based surveys were conducted in the two close by villages at three time points during a single malaria transmission season. Plasmodium carriage in the human populations was determined by Rapid Diagnostic Tests (RDTs), microscopy and real-time PCR. Anthropophilic mosquitoes were captured by human landing captures and presence of Plasmodium sporozoites was assessed by robust Real Time PCR. Overall human malaria prevalence was 8.0% by RDT, 4.8% by microscopy and 11.9% by PCR, mainly due to P. falciparum detected in 92.2% of the PCR positive samples and Plasmodium vivax (5.7%). No significant differences in Plasmodium human carriage was observed between the 2 villages at any time point. Of the 1553 anopheline mosquitoes tested, 13 were found carrying Plasmodium sporozoites, the majority of them being captured outdoor. The mosquito sporozoite indices were not significantly different between the two villages. However, our entomological analysis revealed that Anopheles coustani was the main vector in one village, being responsible of 25.5 infective bites during the whole survey, whereas it was Anopheles arabiensis in the other village with 15 infective bites. In addition, we found a significant higher number of endophagic An. coustani and An. arabiensis in one village compared to the other.Conclusions/SignificanceDespite similar human malaria prevalence in two close by villages, the entomological survey demonstrated the contribution of two different mosquito species in each village, and importantly the role of a suspected secondary malaria vector, An. coustani, as the main vector in one village. This, along with its higher endophagic rate in that village, highlights the importance of combining parasitology and entomology surveys for better targeting the actual local malaria vector. Such study should contribute to the malaria pre-elimination goal established under the 2018-2022 National Malaria Strategic Plan.Author SummaryMalaria is still a major health concern in many countries in sub-Saharan Africa such as Madagascar. In this study, we determined the contribution of malaria vectors in the transmission of Plasmodium parasites in two nearby villages in an area of moderate to high malaria transmission in Madagascar. We collected, during a single malaria transmission season, parasitological data in the human population and entomological data in the mosquito population, in order to evaluate Plasmodium carriage in these two populations. The results showed that despite similarity in human malaria prevalence and in vector species diversity in each village, the contribution of vectors was different between the two villages. An. arabiensis was the major vector in Ambohitromby while it was An. coustani that played this role in Miarinarivo. Importantly, this study is the first that clearly demonstrates that An. coustani could act as a major local vector in Madagascar. Such study should help deploying adapted malaria vector control and contributing to the malaria pre-elimination goal established under the 2018-2022 National Malaria Strategic Plan.


Author(s):  
Mouctar Diallo ◽  
Djibril Sangare ◽  
Assetou Diarra ◽  
Djènèba Camara ◽  
Ramata Mariko ◽  
...  

Malaria vector control strategy is a key component of malaria control, it can interrupt malaria transmission. The effective use of this strategy is based on a depth knowledge of vector life cycle and the environmental factors that influence its life. The aims of this study was to determine the dynamics of the adult population of An.gambiae s.l. and to evaluate the allelic polymorphism of TEP1 gene implicate in malaria parasite lysis.  This was conducted in endemic malaria areas Nanguilabougou and its hamlet of culture Kouroubabougou in the rural commune of Bancoumana between June 2014 and November 2015 during the high malaria transmission season. Mosquitoes were collected using light traps, stored in 50-ml tubes containing ethanol 70%, processed in the laboratory using PCR (DNA extraction, species identification and genotyping).  In 2014 a total of 1433 mosquitoes were collected, An coluzzii was predominant 72.2% (n= 1034) follow by An gambiae 21.1% and hybrid An coluzzii/gambiae 3.1%. The same situation was observed in 2015 with 6612 mosquitoes collected, An coluzzii 72.4% follow by An gambiae 16.7% and hybrid An. coluzzii/gambiae 0.4%. Two An. arabiensis were found only in 2015. A strong presence of the genotype R1/R1 within An. coluzzii 85.2% in 2014 and 66.2% in 2015 was observed. An. gambiae was more associated with the S1/S1 genotype in 2014 and with the S1/R2 allele in 2015. The other allele were founded at low frequency. An. coluzzii is the most predominant during high malaria transmission season among An. gambiae s.l. species. It is also carried the high frequency TEP1 gene implicate in malaria parasite lysis.


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