
Marc VeldhoenInstituto de Medicina Molecular + Faculty of Medicine University of Lisbon
Marc Veldhoen
PhD
About
139
Publications
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Introduction
Marc Veldhoen has a MSc in Medical Biology, Faculty of Medicine, University of Utrecht and a PhD in Immunology obtained at the National Institute for Medical Research (NIMR), London. He did his post-doc at NIMR, working on Thelper cell differentiation. In 2010 he moved to Cambridge to start his own group, with a focus on mucosal T cells. In 2016 he took up the position of ERA Chair at the Instituto de Medicina Molecular, Lisbon, with a continuing focus on mucosal T cell biology.
Additional affiliations
March 2010 - September 2014
June 2006 - February 2010
May 2003 - May 2006
Education
September 1995 - August 2000
Publications
Publications (139)
Preexisting immunity may be associated with increased protection against non-related pathogens such as, SARS-CoV-2. There is little information regarding endemic human coronaviruses (HCOVs) from Pakistan, which experienced a relatively low COVID-19 morbidity and mortality. We investigated antibodies to SARS-CoV-2 and HCoVs NL63 and OC43, comparing...
Objective
Genetic associations and blockade of the interleukin (IL)‐23/IL‐17 axis with monoclonal antibodies support a role for this pathway in patients with psoriatic arthritis (PsA). This study examines the requirement of IL‐23 for IL‐17 production and the role of the metabolic microenvironment in the expansion of Th17‐derived cells in patients w...
[This corrects the article DOI: 10.1371/journal.pone.0271259.].
We have rapidly gained insights into the presence and function of T lymphocytes in non‐lymphoid tissues, the tissue‐resident memory T (T RM ) cells. The central pillar of adaptive immunity has been expanded from classic central memory T cells giving rise to progeny upon reinfection and effector memory cells circulating through the blood and patroll...
Background
Protection against SARS-CoV-2 is mediated by humoral and T cell responses. Pakistan faced relatively low morbidity and mortality from COVID-19 through the pandemic. To examine the role of prior immunity in the population, we studied IgG antibody response levels, virus neutralizing activity and T cell reactivity to Spike protein in a heal...
Immunological memory is critical for immune protection, particularly at epithelial sites, which are under constant risk of pathogen invasions. To counter invading pathogens, CD8⁺ memory T cells develop at the location of infection: tissue-resident memory T cells (TRM). CD8⁺ T-cell responses are associated with type-1 infections and type-1 regulator...
Background and Aims
COVID‐19 vaccinations have reduced morbidity and mortality from the disease. Antibodies against severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) have been associated with immune protection. Seroprevalence studies revealed high immunoglobulin G (IgG) antibody levels to SARS‐CoV‐2 in the Pakistani population before vac...
The emergence of novel variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) underscores the need to investigate alternative approaches to prevent infection and treat patients with coronavirus disease 2019. Here, we report the preclinical efficacy of NL-CVX1, a de novo decoy that blocks virus entry into cells by binding with nano...
Koutsakos et al. have recently published an article showing that SARS-CoV-2 breakthrough infection results in robust naïve and memory T cell activation, and the activity of CD8 T cells strongly correlates with viral clearance.
Long-term solutions against SARS-CoV-2 infections require understanding of immune protection induced by different vaccine COVID-19 formulations. We investigated humoral and cellular immunity induced by Sinopharm (BBIBP-CorV) in a region of high SARS-CoV-2 seroprevalence.
Levels of IgG antibodies to SARS-CoV-2 spike protein and its receptor-binding...
Introduction
An estimated 1.5 million cases were reported in Pakistan until 23 March, 2022. However, SARS-CoV-2 PCR testing capacity has been limited and the incidence of COVID-19 infections is unknown. Volunteer healthy blood donors can be a control population for assessment of SARS-CoV-2 exposure in the population. We determined COVID-19 seroprev...
The metabolic capacity of many cells is tightly regulated and can adapt to changes in metabolic resources according to environmental changes. Tissue-resident memory (TRM) CD8+ T cells are one of the most abundant T cell populations and offer rapid protection against invading pathogens, especially at the epithelia. TRM cells metabolically adapt to t...
Severe malaria can manifest itself with a variety of well-recognized clinical phenotypes that are highly predictive of death – severe anaemia, coma (cerebral malaria), multiple organ failure, and respiratory distress. The reasons why an infected individual develops one pathology rather than another remain poorly understood. Here we use distinct rod...
Introduction
Sinopharm (BBIBP-CorV) inactivated virus vaccination for COVID-19 has been administered widely in Pakistan. We investigated the dynamics of BBIBP-CorV -induced antibody responses over a 24 week period in a region with a high seroprevalence.
Methods
Study subjects (n = 312) were followed up over a 24-week period between May and August...
Objective:
To identify risk factors for SARS-CoV-2 infection and for severe/critical COVID-19, and to assess the humoral response after COVID-19 in these patients.
Methods:
Nationwide study of adult patients with inflammatory RMDs prospectively followed in the Rheumatic Diseases Portuguese Register-Reuma.pt-during the first 6 months of the pande...
We investigated antibody and T cell responses to SARS-CoV-2 in COVID-19 cases and exposed but healthy individuals further compared with pre-pandemic controls in a high infectious disease burden setting.
Levels of IgG antibodies to Spike and RBD strongly correlated in COVID-19 and controls but not in prepandemic cases. IgG to RBD was associated wit...
Non-lymphoid organs, in mice and humans, contain CD8⁺ tissue-resident memory T (TRM) cells. They play important roles in tissue homeostasis as well as defence against infections and cancer. TRM cells have common characteristics that enables their tissue residency and function. However, the wide variety of tissues, some with continually exposure to...
Background
Individuals recovering from COVID-19 are known to have antibodies against the Spike and other structural proteins. Antibodies against Spike have been shown to display viral neutralization. However, not all antibodies against Spike have neutralizing ability although they may be cross-reactive. There is a need for easy-to-use SARS-CoV-2 ne...
During the COVID-19 pandemic, Portugal has experienced three distinct SARS-CoV-2 infection waves. We previously documented the prevalence of SARS-CoV-2 immunity, measured by specific antibodies, in September 2020, six months after the initial moderate wave. Here we show the seroprevalence changes six months later, up to the second week of March 202...
T cells located in non-lymphoid tissues have come to prominence in recent years. CD8+ tissue-resident memory (Trm) cells are important for tissue immune surveillance, provide an important line of defence against invading pathogens and show promise in cancer therapies. These cells differ in phenotype from other memory populations, are adapted to the...
In order to identify risk factors for SARS-CoV-2 infection as well as for severe/critical COVID-19 in rheumatic and musculoskeletal diseases (RMDs) patients, we conducted a multicentre observational nationwide study of adult patients prospectively-followed in the Rheumatic Diseases Portuguese Register - Reuma.pt - during the first 6 months of the p...
Introduction
One million cases of COVID-19 have been reported in Pakistan until August 1, 2021. However, SARS-CoV-2 PCR testing capacity is limited, and the true level of SARS-CoV-2 infections is unknown. Most individuals have asymptomatic or mild COVID-19 and remain undiagnosed. Volunteer healthy blood donors can be a control population for assess...
Background
Individuals recovering from COVID-19 are shown to have antibodies against the Spike and other structural proteins. Antibodies against Spike have been shown to display viral neutralization. However, not all antibodies against Spike have neutralizing ability and some may be cross-reactive. There is a need for easy-to-use SARS-CoV-2 neutral...
In September 2020, we tested 13,398 persons in Portugal for antibodies against severe acute respiratory syndrome coronavirus 2 by using a quota sample stratified by age and population density. We found a seroprevalence of 2.2%, 3-4 times larger than the official number of cases at the end of the first wave of the pandemic.
The unique biology of the intestinal epithelial barrier is linked to a low baseline oxygen pressure (pO2), characterised by a high rate of metabolites circulating through the intestinal blood and the presence of a steep oxygen gradient across the epithelial surface. These characteristics require tight regulation of oxygen homeostasis, achieved in p...
Tryptophan catabolism is a major metabolic pathway utilized by several professional and non-professional antigen presenting cells to maintain immunological tolerance. Here we report that 3-hydroxy-l-kynurenamine (3-HKA) is a biogenic amine produced via an alternative pathway of tryptophan metabolism. In vitro, 3-HKA has an anti-inflammatory profile...
After more than one year since the COVID-19 outbreak, patients with severe disease still constitute the bottleneck of the pandemic management. Aberrant inflammatory responses, ranging from cytokine storm to immune-suppression, were described in COVID-19 and no treatment was demonstrated to change the prognosis significantly. Therefore, there is an...
There is a consensus that mass vaccination against SARS-CoV-2 will ultimately end the COVID-19 pandemic. However, it is not clear when and which control measures can be relaxed during the rollout of vaccination programmes. We investigate relaxation scenarios using an age-structured transmission model that has been fitted to age-specific seroprevale...
During the COVID-19 pandemic, Portugal has experienced three distinct SARS-CoV-2 infection waves. We previously documented the prevalence of SARS-CoV-2 immunity, measured by specific antibodies, in September 2020, six months after the initial moderate wave. Here we show the seroprevalence changes six months later, up to the second week of March 202...
Background:
SARS-CoV-2 infected cancer patients (CP) show worse outcomes compared with non-cancer patients (NCP). The humoral immune response (HIR) of CP against SARS-CoV-2 is not well characterized. To better understand it, we conducted a serological study of hospitalized SARS-CoV-2 CP.
Materials and methods:
Unicentric, retrospective study enr...
There is a consensus that mass vaccination against SARS-CoV-2 will ultimately end the COVID-19 pandemic. However, it is not clear when and which control measures can be relaxed during the rollout of vaccination programmes. We investigate relaxation scenarios using an age-structured transmission model that has been fitted to age-specific seroprevale...
There is a consensus that mass vaccination against SARS-CoV-2 will ultimately end the COVID-19 pandemic. However, it is not clear when and which control measures can be relaxed during the rollout of vaccination programmes. We investigate relaxation scenarios using an age-structured transmission model that has been fitted to age-specific seroprevale...
COVID-19 vaccinations have started. They will stop the pandemic. Citing recent data that are in line with immunological knowledge and predictions, combined with insights of common cold coronaviruses, we here set out the case that the maintenance of population immunity will not depend on continued vaccinations but on the endemic presence of SARS-CoV...
SARS-CoV-2 has emerged as a human pathogen, causing clinical signs, from fever to pneumonia-COVID-19-but may remain mild or asymptomatic. To understand the continuing spread of the virus, to detect those who are and were infected, and to follow the immune response longitudinally, reliable and robust assays for SARS-CoV-2 detection and immunological...
SARS-CoV-2 has emerged as a novel human pathogen, causing clinical signs, from fever to pneumonia - COVID-19 - but may remain mild or even asymptomatic. To understand the continuing spread of the virus, to detect those who are and were infected, and to follow the immune response longitudinally, reliable and robust assays for SARS-CoV-2 detection an...
AhR is a ligand-activated transcription factor that plays an important role in the innate and adaptive immune responses. In infection models, it has been associated with host responses that promote or inhibit disease progression. In pulmonary paracoccidioidomycosis, a primary fungal infection endemic in Latin America, immune protection is mediated...
Immunity relies on tissue surveillance and efficient generation of memory T cells, with differences in recall ability and effector functions providing intersecting levels of immune protection. Tissue-resident memory T (TRM) cells, functionally distinct from circulating memory T cells, have a critical role in protective immunity in tissues, are more...
Class I PI3K enzymes are critical for the maintenance of effective immunity. In T cells, PI3Kα and PI3Kδ are activated by the TCR and costimulatory receptors, whereas PI3Kγ is activated by G protein-coupled chemokine receptors. PI3Kδ is a key regulator of regulatory T (Treg) cell function. PI3K isoform-selective inhibitors are in development for th...
Background:
How intestinal epithelial cells interact with the microbiota and how this is regulated at the gene expression level are critical questions. Smarcad1 is a conserved chromatin remodeling factor with a poorly understood tissue function. As this factor is highly expressed in the stem and proliferative zones of the intestinal epithelium, we...
These guidelines are a consensus work of a considerable number of members of the immunology and flow cytometry community. They provide the theory and key practical aspects of flow cytometry enabling immunologists to avoid the common errors that often undermine immunological data. Notably, there are comprehensive sections of all major immune cell ty...
The gut microbiota influences several biological functions including immune responses. Inflammatory bowel disease is favorably influenced by consumption of several dietary natural plant products such as pomegranate, walnuts, and berries containing polyphenolic compounds such as ellagitannins and ellagic acid. The gut microbiota metabolizes ellagic...
In the past years, there have been significant advances in the understanding of how environmental conditions alone or in conjunction with pathogen invasion affect the metabolism of T cells, thereby influencing their activation, differentiation, and longevity. Detailed insights of the interlinked processes of activation and metabolism can contribute...
Skin-resident T cells protect against invasive microorganisms. A new study reports that commensal-specific type-17 (but not type-1) T cells in the skin are poised to switch to a type-2 response upon tissue injury and contribute to wound repair.
Eimeria vermiformis is a tissue specific, intracellular protozoan that infects the murine small intestinal epithelia, which has been widely used as a coccidian model to study mucosal immunology. This mouse infection model is valuable to investigate the mechanisms of host protection against primary and secondary infection in the small intestine. Her...
Adaptive immunity critically depends on cell migration combined with clonal selection and rapid expansion of rare lymphocytes recognising their cognate antigen in secondary lymphoid organs. It has since become apparent that large populations of T cells are maintained in tissues, which do not migrate throughout the body and do not require clonal exp...
Epithelial-resident T lymphocytes, such as intraepithelial lymphocytes (IELs) located at the intestinal barrier, can offer swift protection against invading pathogens. Lymphocyte activation is strictly regulated because of its potential harmful nature and metabolic cost, and most lymphocytes are maintained in a quiescent state. However, IELs are ke...
The recently discovered histone post-translational modification crotonylation connects cellular metabolism to gene regulation. Its regulation and tissue-specific functions are poorly understood. We characterize histone crotonylation in intestinal epithelia and find that histone H3 crotonylation at lysine 18 is a surprisingly abundant modification i...
Immune-based tumor-therapy has seen substantial progress in recent years and has made important inroads in the fight against cancer. Checkpoint inhibitors are a clinical success and the use of cell-based therapy models is rapidly expanding. T cells, such as chimeric antigen receptor T cells (CARs) and tumor infiltrating lymphocytes (TILs), are now...
BackgroundDNA methylation changes at a discrete set of sites in the human genome are predictive of chronological and biological age. However, it is not known whether these changes are causative or a consequence of an underlying ageing process. It has also not been shown whether this epigenetic clock is unique to humans or conserved in the more expe...
The trillions of microorganisms that reside in the gastrointestinal tract, essential for nutrient absorption, are kept under control by a single cell barrier and large amounts of immune cells. Intestinal epithelial cells (IECs) are critical in establishing an environment supporting microbial colonization and immunological tolerance. A large populat...
T helper-17 (Th17) cells are associated with inflammatory disorders and cancer. We report that environmental conditions resulting in cellular stress, such as low oxygen, glucose, and isotonic stress, particularly enhance the generation of Th17 cells. Pharmacological inhibition of cell stress reduces Th17 cell differentiation while stress inducers e...
Increased understanding of the biology of interleukin 17 (IL-17) has revealed that this cytokine is a central player in immunity at the sites most exposed to microorganisms. Although it has been strongly associated with immunopathology, IL-17 also has an important role in host defense. The regulation of IL-17 secretion seems to be shared among vari...
The gastrointestinal tract is continuously exposed to many environmental factors that influence intestinal epithelial cells and the underlying mucosal immune system. In this article, we demonstrate that dietary fiber and short chain fatty acids (SCFAs) induced the expression of the vitamin A-converting enzyme RALDH1 in intestinal epithelial cells i...
How immunity is regulated at distinct epithelial tissues that vary in microbial occupancy and environmental and tissue specific cues isn't clear. Dutzan et al. (2017) report that mechanical-derived signals, not those from micro-organisms, are key to maintaining interleukin-17-expressing T helper (Th17) cells at the oral epithelia.
The discovery of Th17 cell plasticity, in which CD4(+) IL-17-producing Th17 cells give rise to IL-17/IFN-γ double-producing cells and Th1-like IFNγ(+) ex-Th17 lymphocytes, has raised questions regarding which of these cell types contribute to immunopathology during inflammatory diseases. In this study, we show using Helicobacter hepaticus-induced i...