A5022424808- Malaria Research and Control
- Mosquito-borne diseases and control
- Complement system in diseases
- T-cell and B-cell Immunology
- HIV Research and Treatment
- Immune Cell Function and Interaction
- Iron Metabolism and Disorders
- Hemoglobinopathies and Related Disorders
- Drug Transport and Resistance Mechanisms
- Parasites and Host Interactions
- Aquaculture disease management and microbiota
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Hepatitis B Virus Studies
- Heme Oxygenase-1 and Carbon Monoxide
- Vibrio bacteria research studies
- Vector-borne infectious diseases
- Cannabis and Cannabinoid Research
- Travel-related health issues
- Escherichia coli research studies
- vaccines and immunoinformatics approaches
- Invertebrate Immune Response Mechanisms
- Trypanosoma species research and implications
- Immunotherapy and Immune Responses
- Parasite Biology and Host Interactions
- Multiple Myeloma Research and Treatments
Max Planck Institute for Infection Biology
2021-2025
National Institutes of Health
2012-2024
National Institute of Allergy and Infectious Diseases
2012-2024
University Hospital Heidelberg
2016-2024
Heidelberg University
2016-2024
Frederick National Laboratory for Cancer Research
2024
German Center for Infection Research
2020-2022
Immungenetics (Germany)
2014
Max Planck Society
2014
University of Lisbon
2006-2011
Glycosylation processes are under high natural selection pressure, presumably because these can modulate resistance to infection. Here, we asked whether inactivation of the UDP-galactose:β-galactoside-α1-3-galactosyltransferase (α1,3GT) gene, which ablated expression Galα1-3Galβ1-4GlcNAc-R (α-gal) glycan and allowed for production anti-α-gal antibodies (Abs) in humans, confers protection against Plasmodium spp. infection, causative agent malaria a major driving force human evolution. We...
Protective antibodies in Plasmodium falciparum malaria are only acquired after years of repeated infections. Chronic exposure is associated with a large increase atypical memory B cells (MBCs) that resemble expanded variety persistent viral Understanding the function MBCs and their relationship to classical will be critical developing effective vaccines for other chronic We show VH gene repertoires somatic hypermutation rates indistinguishable indicating common developmental history....
Humoral immunity consists of pre-existing antibodies expressed by long-lived plasma cells and rapidly reactive memory B (MBC). Recent studies MBC development function after protein immunization have uncovered significant heterogeneity. To clarify functional roles for distinct subsets during malaria infection, we generated tetramers that identify Plasmodium-specific MBCs in both humans mice. Long-lived murine consisted three populations: somatically hypermutated immunoglobulin M+ (IgM+) IgG+...
Malaria-specific antibody responses are short lived in children, leaving them susceptible to repeated bouts of febrile malaria. The cellular and molecular mechanisms underlying this apparent immune deficiency poorly understood. Recently, T follicular helper (Tfh) cells have been shown play a critical role generating long-lived responses. We show that Malian children resting PD-1+CXCR5+CD4+ Tfh circulation resemble germinal center phenotypically functionally. Within population,...
BackgroundSubcutaneous administration of the monoclonal antibody L9LS protected adults against controlled Plasmodium falciparum infection in a phase 1 trial. Whether administered subcutaneously can protect children from P. region where this organism is endemic unclear.MethodsWe conducted 2 trial Mali to assess safety and efficacy subcutaneous 6 10 years age over 6-month malaria season. In part A trial, was assessed at three dose levels adults, followed by assessment two children. B were...
Abstract Genomic surveillance of Plasmodium falciparum malaria can provide policy-relevant information about antimalarial drug resistance, diagnostic test failure, and the evolution vaccine targets. Yet large low complexity genome P. complicates development genomic methods, while resource constraints in endemic regions limit their deployment. Here, we demonstrate an approach for targeted nanopore sequencing from dried blood spots (DBS) that enables cost-effective low-resource settings. We...
In malaria-naïve individuals, Plasmodium falciparum infection results in high levels of parasite-infected red blood cells (iRBCs) that trigger systemic inflammation and fever. Conversely, individuals endemic areas who are repeatedly infected often asymptomatic have low iRBCs, even young children. We hypothesized febrile malaria alters the immune system such P. re-exposure reduced production pro-inflammatory cytokines/chemokines enhanced anti-parasite effector responses compared to induced...
Many chronic infections, including malaria and HIV, are associated with a large expansion of CD21-CD27- 'atypical' memory B cells (MBCs) that exhibit reduced cell receptor (BCR) signaling effector functions. Little is known about the conditions or transcriptional regulators driving atypical MBC differentiation. Here we show MBCs in malaria-exposed individuals highly express transcription factor T-bet, T-bet expression correlates inversely BCR skews toward IgG3 class switching. Moreover,...
Malaria remains one of the greatest burdens to global health, causing nearly 500,000 deaths in 2014. When manifesting lungs, severe malaria causes acute lung injury/acute respiratory distress syndrome (ALI/ARDS). We have previously shown that a proportion DBA/2 mice infected with Plasmodium berghei ANKA (PbA) develop ALI/ARDS and these recapitulate various aspects human syndrome, such as pulmonary edema, hemorrhaging, pleural effusion hypoxemia. Herein, we investigated role neutrophils...
Multiplexed PCR amplicon sequencing (AmpSeq) is an increasingly popular application for cost-effective monitoring of threatened species and managed wildlife populations, shows strong potential the genomic epidemiology infectious disease. AmpSeq data from microbes can inform disease control in multiple ways, such as by measuring drug resistance marker prevalence, distinguishing imported local cases, determining effectiveness therapeutics. We describe design comparative evaluation two new...
Chronic asymptomatic Plasmodium falciparum infections are common in endemic areas and thought to contribute the maintenance of malaria immunity. Whether treatment these increases subsequent risk clinical episodes is unclear.In a 3-year study Mali, individuals with or without P. infection at end 6-month dry season were identified by polymerase chain reaction (PCR), was compared during ensuing transmission season. At second season, 3 groups children identified: (1) infected as detected rapid...
IgG antibodies play a role in malaria immunity, but whether and how IgM protects from the biology of Plasmodium falciparum (Pf)–specific B cells is unclear. In Mali cohort spanning infants to adults, we conducted longitudinal analyses Pf- influenza-specific cells. We found that Pf-specific memory (MBCs) are disproportionally IgM+ only gradually shift IgG+ with age, contrast MBCs predominantly infancy adulthood. cell receptor analysis showed somatically hypermutated at levels comparable...
Multimeric immunoglobulin-like molecules arose early in vertebrate evolution, yet the unique contributions of multimeric IgM antibodies to infection control are not well understood. This is partially due difficulty distinguishing low-affinity IgM, secreted rapidly by plasmablasts, from high-affinity derived later-arising memory cells. We developed a pipeline express B cell receptors (BCRs) Plasmodium falciparum–specific IgM+ and IgG+ human cells (MBCs) as both IgG molecules. BCRs subsets...
Abstract Following Plasmodium falciparum infection, individuals can remain asymptomatic, present with mild fever in uncomplicated malaria cases, or show one more severe symptoms. Several studies have investigated associations between parasite transcription and clinical severity, but no broad conclusions yet been drawn. Here, we apply a series of bioinformatic approaches based on P. ’s tightly regulated transcriptional pattern during its ~48-hour intraerythrocytic developmental cycle (IDC) to...
ABSTRACT Host iron deficiency is protective against severe malaria as the human parasite Plasmodium falciparum depends on bioavailable from its host to proliferate. The essential pathways of acquisition, storage, export, and detoxification in differ those humans, orthologs mammalian transferrin receptor, ferritin, or ferroportin, a functional heme oxygenase are absent P. . Thus, proteins involved these processes may be excellent targets for therapeutic development, yet remain largely...
Whether jaundice, a common presentation of Plasmodium ( P .) falciparum malaria (1-3) arising from the accumulation circulating bilirubin, represents an adaptive or maladaptive response to spp. infection is not understood (1-3). We found that asymptomatic P. was associated with >10-fold higher ratio unconjugated bilirubin over parasite burden, compared symptomatic malaria. Genetic suppression synthesis by biliverdin reductase A (BVRA) (4) increased virulence and mortality in mice....