A5017711874- Parasites and Host Interactions
- Parasite Biology and Host Interactions
- Helminth infection and control
- Immunotherapy and Immune Responses
- Mosquito-borne diseases and control
- Insect symbiosis and bacterial influences
- Immune Cell Function and Interaction
- Immune cells in cancer
- Gut microbiota and health
- T-cell and B-cell Immunology
- Immune Response and Inflammation
- IL-33, ST2, and ILC Pathways
- Extracellular vesicles in disease
- Invertebrate Immune Response Mechanisms
- Parasitic Diseases Research and Treatment
- MXene and MAX Phase Materials
- Cancer Cells and Metastasis
- Bat Biology and Ecology Studies
- Nematode management and characterization studies
- Vitamin C and Antioxidants Research
- Autophagy in Disease and Therapy
- Microfluidic and Bio-sensing Technologies
- 3D Printing in Biomedical Research
- Tuberculosis Research and Epidemiology
- Animal Behavior and Reproduction
Wellcome Sanger Institute
2016-2025
University of Cambridge
2022-2025
Wellcome/MRC Cambridge Stem Cell Institute
2023-2025
Stem Cell Institute
2024
Connecticut Agricultural Experiment Station
2018-2020
Max Planck Institute for Infection Biology
2011-2017
Yale University
2016-2017
Max Planck Society
2014
Universidad de Antioquia
2006-2012
Mayo Clinic in Arizona
2009-2011
As a hallmark of tuberculosis (TB), Mycobacterium (MTB) induces granulomatous lung lesions and systemic inflammatory responses during active disease. Molecular regulation inflammation is associated with inflammasome assembly. We determined the extent to which MTB triggers activation how this impacts on severity TB in mouse model. stimulated release mature IL-1β macrophages while attenuated M. bovis BCG failed do so. Tubercle bacilli specifically activated NLRP3 propensity was strictly...
Significance Tuberculosis (TB) granulomas represent sites of both bacterial containment and tissue pathology. Macrophage killing Mycobacterium tuberculosis ( Mtb ) in to contain infection must be regulated prevent collateral damage. Nitric oxide synthase-2 (NOS2) arginase-1 (Arg1), macrophage enzymes metabolizing l -arginine, play key roles this process. NOS2 produces reactive nitrogen intermediates kill , whereas Arg1 regulates activity via substrate competition. could predominate hypoxic...
Abstract The mosquito gut microbiome plays an important role in development and fitness, providing a promising avenue for novel control strategies. Here we present method rearing axenic (bacteria free) Aedes aegypti mosquitoes, consisting of feeding sterilized larvae on agar plugs containing high concentration liver yeast extract. This approach allows the complete to adulthood while maintaining sterility; however, mosquito’s exhibit delayed time stunted growth comparison their bacterially...
Over the last decade, research interest in defining how extracellular vesicles (EVs) shape cross-species communication has grown rapidly. Parasitic helminths, worm species found phyla Nematoda and Platyhelminthes, are well-recognised manipulators of host immune function physiology. Emerging evidence supports a role for helminth-derived EVs these processes highlights as an important participant cross-phylum communication. While mammalian EV field is guided by community-agreed framework...
Regulatory T cells (T reg cells) are characterized by the expression of forkhead lineage-specific transcription factor Foxp3, and their main function is to suppress cells. While evaluating cells, we identified a population Foxp3-positive that were CD11b(+)F4/80(+)CD68(+), indicating macrophage origin. These observed in spleen, lymph nodes, bone marrow, thymus, liver, other tissues naive animals. To characterize this subpopulation macrophages, devised strategy purify CD11b(+)F4/80(+)Foxp3(+)...
Enteric fever, caused by Salmonella enterica serovar Typhi, is an important public health problem in resource-limited settings and, despite decades of research, human responses to the infection are poorly understood. In 41 healthy adults experimentally infected with wild-type S. we detected significant cytokine within 12 h bacterial ingestion. These early did not correlate subsequent clinical disease outcomes and likely indicate initial host–pathogen interactions gut mucosa. participants...
Whipworms are large metazoan parasites that inhabit multi-intracellular epithelial tunnels in the intestine of their hosts, causing chronic disease humans and other mammals. How first-stage larvae invade host epithelia establish infection remains unclear. Here we investigate early events using both Trichuris muris infections mice murine caecaloids, first in-vitro system for whipworm organoid model live helminths. We show degrade mucus layers to access cells. In syncytial tunnels, completely...
Whipworms ( Trichuris spp) are ubiquitous parasites of humans and domestic wild mammals that cause chronic disease, considerably impacting human animal health. Egg hatching is a critical phase in the whipworm life cycle marks initiation infection, with newly hatched larvae rapidly migrating to invading host intestinal epithelial cells. Hatching triggered by microbiota; however, physical chemical interactions between bacteria eggs, as well bacterial larval responses result disintegration...
Highlights•Individual T helper cells commit to produce distinct amounts of a given cytokine•The magnitude T-bet expression controls cell's amount IFN-γ production•Single Th1 memory recall the production individual and amounts•Graded bacterial killing by macrophagesSummaryThe probabilistic cytokine genes in differentiated (Th) cell populations remains ill defined. By single-cell analyses mathematical modeling, we show that one stimulation featured stable nonproducers as well producers with...
Whole genome sequencing is being rapidly applied to the study of helminth genomes, including de novo assembly, population genetics, and diagnostic applications. Although late-stage juvenile adult parasites typically produce sufficient DNA for molecular analyses, these parasitic stages are almost always inaccessible in live host; immature life found environment which samples can be collected non-invasively offer a potential alternative, however, yield very low quantities DNA, environmentally...
T cell responses are compromised in the elderly. The B7-CD28 family receptors critical regulation of immune responses. We evaluated whether B7-family and CD28-family were differentially expressed dendritic cells, macrophages, CD4(+) CD8(+) cells from young old mice, which could contribute to dysfunction old. Although most equally all >85% naive B7-H1 compared with 25% young. Considering that negatively regulates responses, we hypothesized expression would downregulate function cells. Old...
The molecular basis of pathogen-induced host cell apoptosis is well characterized for a number microorganisms. Mycobacterium tuberculosis known to induce and it was shown that live but not heat killed M. stimulates this biological pathway in monocytes. dependence activity on bacilli led us hypothesize products released or secreted by are the primary apoptotic factors human Thus, culture filtrate vitro grown strain H37Rv fractioned conventional chromatography apoptosis-inducing individual...
The whipworm Trichuris trichiura is a soil-transmitted helminth that dwells in the epithelium of caecum and proximal colon their hosts causing human disease, trichuriasis. Trichuriasis characterized by colitis attributed to inflammatory response elicited parasite while tunnelling through intestinal epithelial cells (IECs). IL-10 family receptors, comprising combinations subunits IL-10Rα, IL-10Rβ, IL-22Rα IL-28Rα, modulates responses. Here we carefully dissected role these resistance mice...
The caecum, an intestinal appendage in the junction of small and large intestines, displays a unique epithelium that serves as exclusive niche for range pathogens including whipworms (Trichuris spp.). While protocols to grow organoids from intestine (enteroids) colon (colonoids) exist, conditions culture caecum have yet be described. Here, we report methods grow, differentiate characterise mouse adult stem cell-derived caecal organoids, termed caecaloids. We compare cellular composition...
Macroautophagy is an evolutionarily conserved cellular process critical for maintaining homeostasis. It can additionally function as innate immune response to viral infection has been demonstrated a number of arthropod-borne (arbo-) viruses. Arboviruses are maintained in transmission cycle between vertebrate hosts and invertebrate vectors yet the majority studies assessing autophagy-arbovirus interactions have limited mammalian host. Therefore we evaluated role autophagy during arbovirus...
The microbiome is an assemblage of microorganisms living in association with a multicellular host. Numerous studies have identified role for the host physiology, development, immunity, and behaviour. generation axenic (germ-free) gnotobiotic model systems has been vital to dissecting biology. We previously reported Aedes aegypti mosquitoes, primary vector several human pathogenic viruses, including dengue virus Zika virus. In order better understand influence on we examined transcriptomes...
Abstract The immune response of splenic cells to SRBC and LPS or Con A mitogens is suppressed in P. chabaudi-infected mice. When mixed with from normal donors, spleen infected mice also anti-SRBC mitogenic responses. Suppression was not detected lymph node cells, bone marrow, thymocytes Removal red had no effect on suppression. cell population responsible for the suppressive activity adherent plastic, resistant irradiation anti-Thy-1 plus complement treatment.
Gastrointestinal nematodes are a diverse class of pathogens that colonise quarter the world’s human population and nearly all grazing livestock. These macroparasites establish, some migrate, within host gastrointestinal niches during their life cycles release molecules condition mucosa to enable chronic infections. Understanding how helminths do this, defining mechanisms involved in modulation, holds promise for novel strategies anthelmintics vaccines, as well new knowledge immune regulation...
Abstract During active TB in humans a spectrum of pulmonary granulomas with central necrosis and hypoxia exists. BALB/c mice, predominantly used drug development, do not reproduce this complex pathology thereby inaccurately predicting clinical outcome. We found that Nos2 −/− mice incapable NO-production immune cells as microbial defence uniformly develop hypoxic necrotizing lung lesions, widely observed human TB. To study the impact on efficacy antimycobacterials candidates, we subjected to...