A5008912785- Malaria Research and Control
- Mosquito-borne diseases and control
- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Parasites and Host Interactions
- Complement system in diseases
- Viral Infections and Vectors
- vaccines and immunoinformatics approaches
- Invertebrate Immune Response Mechanisms
- Immunotherapy and Immune Responses
- HIV Research and Treatment
- Tuberculosis Research and Epidemiology
- Research on Leishmaniasis Studies
- Zoonotic diseases and public health
- COVID-19 epidemiological studies
- Travel-related health issues
- Vector-borne infectious diseases
- Bacteriophages and microbial interactions
- Aquaculture disease management and microbiota
- Mycobacterium research and diagnosis
- Parasitic Diseases Research and Treatment
- Bat Biology and Ecology Studies
- interferon and immune responses
- Antibiotic Resistance in Bacteria
- Hepatitis B Virus Studies
University of London
2007-2025
London School of Hygiene & Tropical Medicine
2014-2025
Noguchi Memorial Institute for Medical Research
2023
University of Ghana
2023
Biology of Infection
2018
Max Planck Institute for Infection Biology
2011
Max Planck Society
2011
New York University
2001-2007
Johns Hopkins University
2005
Research Institute for Tropical Medicine
1997-2001
Intracellular bacteria and parasites typically invade host cells through the formation of an internalization vacuole around invading pathogen. Plasmodium sporozoites, infective stage malaria parasite transmitted by mosquitoes, have alternative mechanism to enter cells. We observed breaching plasma membrane cell followed rapid repair. This mode entry did not result in a sporozoite, was exit from cell. Sporozoites traversed cytosol several before hepatocyte parasitophorous vacuole, which they...
Abstract The laboratory mouse is the workhorse of immunology, used as a model mammalian immune function, but how well responses mice reflect those free-living animals unknown. Here we comprehensively characterize serological, cellular and functional parameters wild compare them with mice, finding that systems are, comparatively, in highly activated (primed) state. Associations between infection suggest high level pathogen exposure drives this activation. Moreover, have population myeloid...
Antibodies constitute a critical component of the naturally acquired immunity that develops following frequent exposure to malaria. However, specific antibody titres have been reported decline rapidly in absence reinfection, supporting widely perceived notion malaria infections fail induce durable immunological memory responses. Currently, direct evidence for presence or immune is limited. In this study, we analysed longevity both and B cell responses antigens among individuals who were...
Resistance to several prevalent infectious diseases requires both cellular and humoral immune responses. T cell immunity is initiated by mature dendritic cells (DCs) in lymphoid organs, whereas responses most antigens require further collaboration between primed, antigen-specific helper naive or memory B cells. To determine whether delivered DCs organs induce help for antibody responses, we targeted a carrier protein, ovalbumin (OVA), the presence of maturation stimulus assayed antibodies...
The outcome of malaria infection is determined, in part, by the balance pro-inflammatory and regulatory immune responses. Failure to develop an effective response can lead unrestricted parasite replication, whilst failure regulate this leads development severe immunopathology. IL-10 TGF-beta are known be important components response, but cellular source these cytokines still unknown. Here we have examined role natural adaptive T cells control find that classical CD4+CD25(hi) (and Foxp3+) do...
There is considerable debate as to the nature of primary parasite-derived moieties that activate innate pro-inflammatory responses during malaria infection. Microparticles (MPs), which are produced by numerous cell types following vesiculation cellular membrane a consequence death or immune-activation, exert strong activity in other disease states. Here we demonstrate MPs, derived from plasma infected mice, but not naive induce potent activation macrophages vitro measured CD40 up-regulation...
It is well established that IFN-γ required for the development of experimental cerebral malaria (ECM) during Plasmodium berghei ANKA infection C57BL/6 mice. However, temporal and tissue-specific cellular sources P. have not been investigated, it known whether production by a single cell type in isolation can induce pathology. In this study, using reporter mice, we show NK cells dominate response early stages brain, but spleen, before being replaced CD4(+) CD8(+) T cells. Importantly,...
Malaria-infected mice treated with antibiotics remain healthy and are protected against subsequent malaria infection.
The balance between pro-inflammatory and regulatory immune responses in determining optimal T cell activation is vital for the successful resolution of microbial infections. This maintained part by negative regulators activation, CTLA-4 PD-1/PD-L, which dampen effector during chronic However, their role acute infections, such as malaria, remains less clear. In this study, we determined contribution PD-1/PD-L to regulation Plasmodium berghei ANKA (PbA)-induced experimental cerebral malaria...
Data from a variety of experimental models suggest that natural killer (NK) cells require signals accessory in order to respond optimally pathogens, but the precise identity able provide such depends upon nature infectious organism. Here we show ability human NK produce interferon-γ response stimulation by Plasmodium falciparum–infected red blood (iRBCs) is strictly dependent multiple, contact-dependent and cytokine-mediated derived both monocytes myeloid dendritic (mDCs). Contrary some...
Successful resolution of malaria infection requires induction proinflammatory immune responses that facilitate parasite clearance; however, failure to regulate this inflammation leads immune-mediated pathology. The pathways maintain immunological balance during remain poorly defined. In study, we demonstrate IL-27R-deficient (WSX-1(-/-)) mice are highly susceptible Plasmodium berghei NK65 infection, developing exacerbated Th1-mediated responses, which, despite efficient clearance, lead...
Abstract The immune function of wild animals has been rather little studied. Wild animals’ may differ from that laboratory bred because their different environments. This idea follows the concept resource partitioning in which distribute scarce resources to all aspects life, including costly responses. A logical extension this is there be substantial interindividual variation animals. To begin investigate this, we compared a mouse strain (C57BL/6, widely used makes potent responses) and...
RTS,S/AS01, a vaccine targeting pre-erythrocytic stages of Plasmodium falciparum, is undergoing clinical trials. We report an analysis cellular immune response to component Ags RTS,S-hepatitis B surface Ag (HBs) and P. falciparum circumsporozoite (CS) protein-among Tanzanian children in phase IIb RTS,S/AS01(E) trial. RTS,S/AS01 (E) vaccinees make stronger T cell IFN-γ, CD69, CD25 responses HBs peptides than do controls, indicating that RTS,S boosts pre-existing responses. CD69 CS CS-specific...
We generated T cell receptor transgenic mice specific for the liver stages of rodent malaria parasite Plasmodium yoelii and studied early events in development vivo effector functions antigen-specific CD8+ cells. Differently to activated/memory cells, naive cells are not capable exerting antiparasitic activity unless previously primed by immunization. While need differentiate before achieving status, time required this process is very short. Indeed, interferon (IFN)-γ perforin mRNA...
We report that complete protection against malaria and total inhibition of liver stage development parasitemia was obtained in 100% BALB/c mice primed with a replication-defective recombinant adenovirus expressing the circumsporozoite (CS) protein Plasmodium yoelii (AdPyCS), followed by booster an attenuated vaccinia virus, same antigen, VacPyCS. found increased levels activated CS-specific CD8(+) CD4(+) T cells, higher anti-sporozoite antibody titers, greater these mice, when time between...
To track malaria parasites for biological studies within the mosquito and mammalian hosts, we constructed a stably transformed clonal line of Plasmodium berghei, PbFluspo, in which sporogonic pre-erythrocytic liver-stage are autonomously fluorescent. A cassette containing structural gene FACS-adapted green fluorescent protein mutant 2 (GFPmut2), expressed from 5' 3' flanking sequences circumsporozoite (CS) gene, was integrated at endogenous CS locus. Recombinant parasites, bear wild-type...
ABSTRACT In most models of blood-stage malaria infection, proinflammatory immune responses are required for control infection and elimination parasites. We hypothesized therefore that the fulminant infections caused in mice by lethal strain Plasmodium yoelii (17XL) might be due to failure activate a sufficient inflammatory response. Here we have compared adaptive CD4 + T-cell innate response P. 17XL with induced self-resolving, nonlethal , 17X(NL). During first 7 9 days splenic effector were...
Background Malaria caused by Plasmodium falciparum remains a major cause of death in sub-Saharan Africa. Immunity against symptoms malaria requires repeated exposure, suggesting either that the parasite is poorly immunogenic or development effective immune responses to may be impaired. Methods We carried out two age-stratified cross-sectional surveys anti-malarial humoral Gambian village where P. transmission low and sporadic. Circulating antibodies memory B cells (MBC) four malarial...