Andres Vallejo

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Verified

Andres verified their affiliation via an institutional email.

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• PhD
• Professor (Associate) at University of Southampton

Langerhans cells (LCs) in the epidermis present MHC I and MHC II-restricted antigens thereby priming either CD8 or CD4 T cell immune responses. The genomic programs and transcription factors regulating antigen presentation in LCs remain to be elucidated. We show human LCs are highly efficient in MHC I-antigen cross-presentation but lack the transcr...

Single-cell transcriptomics has sensitivity limits that restrict low abundance transcript identification, affects clustering and introduce artefact. Here, we describe Constellation DropSeq (C-DropSeq), a molecular transcriptome filter that delivers two orders of magnitude sensitivity gains by maximising read utility while reducing sequencing depth...

FFPE (formalin-fixed, paraffin-embedded) tissue archives are the largest repository of clinically annotated human specimens. Despite numerous advances in technology, current methods for sequencing of FFPE-fixed single-cells are slow, labour intensive, insufficiently sensitive and have a low resolution, making it difficult to fully exploit their eno...

Novel biomarkers to identify infectious patients transmitting Mycobacterium tuberculosis are urgently needed to control the global tuberculosis (TB) pandemic. We hypothesized that proteins released into the plasma in active pulmonary TB are clinically useful biomarkers to distinguish TB cases from healthy individuals and patients with other respira...

Formalin-fixed paraffin-embedded (FFPE) samples are valuable but underutilized in single-cell omics research due to their low RNA quality. In this study, leveraging a recent advance in single-cell genomic technology, we introduce snPATHO-seq, a versatile method to derive high-quality single-nucleus transcriptomic data from FFPE samples. We benchmar...

Langerhans cells (LCs) are distinct among phagocytes, functioning both as embryo-derived, tissue-resident macrophages in skin innervation and repair and as migrating professional antigen-presenting cells, a function classically assigned to dendritic cells (DCs). Here, we demonstrate that both intrinsic and extrinsic factors imprint this dual identi...

Matrix stiffening by lysyl oxidase-like 2 (LOXL2)-mediated collagen cross-linking is proposed as a core feedforward mechanism that promotes fibrogenesis. Failure in clinical trials of simtuzumab (the humanized version of AB0023, a monoclonal antibody against human LOXL2) suggested that targeting LOXL2 may not have disease relevance; however, target...

BACKGROUND Novel biomarkers to identify infectious patients transmitting Mycobacterium tuberculosis are urgently needed to control the global tuberculosis (TB) pandemic. We hypothesized that proteins released into the plasma in active pulmonary TB are clinically useful biomarkers to distinguish TB cases from healthy individuals and patients with ot...

Pancreatic acinar cells are responsible for producing large amounts of digestive enzymes, which are essential for nutrient breakdown but make it difficult to capture the transcriptome of individual cells. To address this challenge, we use a reversible fixative that is compatible with 10X Genomics, thereby preserving the acinar transcriptome and cap...

Langerhans cells (LCs) are a unique population of phagocytes programmed within embryonic skin to maintain tissue and immunological homeostasis at the epidermal barrier site. Unique amongst tissue-resident macrophages, LCs play roles in skin innervation and repair, while also functioning as migrating professional antigen presenting cells, a capabili...

Despite anti-tuberculous treatment (ATT), central nervous system tuberculosis (CNS-TB) still cause permanent neurological deficits and death. To identify prognostic factors, we profiled a prospective cohort of tuberculous meningitis (TBM) and non-TBM patients. We determined significantly increased cerebrospinal fluid (CSF) matrix metalloproteinases...

Regulation of cutaneous immunity is severely compromised in inflammatory skin disease. To investigate the molecular crosstalk underpinning tolerance versus inflammation in atopic dermatitis, we utilise a human in vivo allergen challenge study, exposing atopic dermatitis patients to house dust mite. Here we analyse transcriptional programmes at the...

Mycobacterium tuberculosis (Mtb) is one of the most successful human pathogens and remains a leading cause of death from infectious disease. Interferon-γ (IFN-γ) is a central regulator of the immune defense against Mtb. Several cytokines have been shown to increase virulence of other bacterial pathogens, leading us to investigate whether IFN-γ has...

Background: Acute cutaneous inflammation causes microbiome alterations as well as ultrastructural changes in epidermis stratification. However, the interactions between keratinocyte proliferation and differentiation status and the skin microbiome have not been fully explored. Objectives: Hypothesizing that the skin microbiome contributes to regu...

Human epidermal Langerhans cells (LCs) maintain immune homeostasis in the skin. To examine transcriptional programming of human primary LCs during homeostasis, we performed scRNA-seq analysis of LCs before and after migration from the epidermis, coupled with functional assessment of their regulatory T cell priming capabilities. The analysis reveale...

Background The COVID-19 pandemic has created pressure on healthcare systems worldwide. Tools that can stratify individuals according to prognosis could allow for more efficient allocation of healthcare resources and thus improved patient outcomes. It is currently unclear if blood gene expression signatures derived from patients at the point of admi...

NK cells are promising cellular therapeutics against hematological and solid malignancies. Immunogenetic studies have identified that various activating killer cell Ig-like receptors (KIRs) are associated with cancer outcomes. Specifically, KIR2DS2 has been associated with reduced incidence of relapse following transplant in hematological malignanc...

One of the most severe forms of cutaneous adverse drug reactions is 'drug reaction with eosinophilia and systemic symptoms' (DRESS), hence subsequent avoidance of the causal drug is imperative. However, attribution of drug culpability in DRESS is challenging and standard skin allergy tests are not recommended due to patient safety reasons. Whilst i...

Leishmania amazonensis and Leishmania major are the causative agents of cutaneous and mucocutaneous diseases. The infections‘ outcome depends on host–parasite interactions and Th1/Th2 response, and in cutaneous form, regulation of Th17 cytokines has been reported to maintain inflammation in lesions. Despite that, the Th17 regulatory scenario remain...

The worldwide COVID-19 pandemic has claimed millions of lives and has had a profound effect on global life. Understanding the body’s immune response to SARS-CoV-2 infection is crucial in improving patient management and prognosis. In this study we compared influenza and SARS-CoV-2 infected patient cohorts to identify distinct blood transcript abund...

T cell pathology in the skin leads to monocyte influx, but we have little understanding of the fate of recruited cells within the diseased niche, or the long-term impact on cutaneous immune homeostasis. By combining a murine model of acute graft-versus-host disease (aGVHD) with analysis of patient samples, we demonstrate that pathology initiates de...

The ability to reliably predict and infer cellular responses to environmental exposures would offer a major advance in the investigation of immune regulation in health and disease. One possible approach is the use of in silico modelling. Design of such a mathematical kinetic model would be based on existing knowledge of a biological system and util...

Mycobacterium tuberculosis (Mtb) is one of the most successful human pathogens and remains a leading cause of death from infectious disease. Interferon-γ (IFN-γ) is a central regulator of the immune defense against Mtb . Several cytokines have been shown to increase virulence of other bacterial pathogens, leading us to investigate whether IFN-γ has...

The global burden of tuberculosis (TB) continues at pandemic proportions, currently with a quarter of the world’s population infected with Mycobacterium tuberculosis (Mtb), and 1.4 million people dying from TB in 2019 (WHO, 2020). Mtb has undergone prolonged co-evolution with humans, with the balance between protective and pathological host respons...

Accurate regulation of cutaneous immunity is fundamental for human health and quality of life but is severely compromised in inflammatory skin disease. To investigate the molecular crosstalk underpinning tolerance vs inflammation in human skin, we set up a human in vivo allergen challenge study, exposing patients with atopic dermatitis (AD) to hous...

The future of single cell diversity screens involves ever-larger sample sizes, dictating the need for higher throughput methods with low analytical noise to accurately describe the nature of the cellular system. Current approaches are limited by the Poisson statistic, requiring dilute cell suspensions and associated losses in throughput. In this co...

p>The future of single cell diversity screens involves ever-larger sample sizes, dictating the need for higher throughput methods with low analytical noise to accurately describe the nature of the cellular system. Current approaches are limited by the Poisson statistic, requiring dilute cell suspensions and associated losses in throughput. In this...

Langerhans cells (LCs) reside in the epidermis as a dense network of immune system sentinels, coordinating both immunogenic and tolerogenic immune responses. To determine molecular switches directing induction of LC immune activation, we performed mathematical modelling of gene regulatory networks identified by single cell RNA sequencing of LCs exp...

Background: Matrix metalloproteinases (MMPs) are implicated as key regulators of tissue destruction in tuberculosis (TB) and may be a target for host-directed therapy. Here, we conducted a Phase 2 randomized, double-blind, placebo-controlled trial investigating doxycycline, a licensed broad spectrum MMP inhibitor, in pulmonary TB patients. Method...

Tuberculosis (TB) is a persistent global pandemic and standard treatment has not changed for thirty years. Mycobacterium tuberculosis (Mtb) has undergone prolonged co-evolution with humans, and patients can control Mtb even after extensive infection, demonstrating the fine balance between protective and pathological host responses within infected g...

Background Natural killer (NK) cells are increasingly being recognized as agents for cancer immunotherapy. The killer cell immunoglobulin-like receptors (KIRs) are expressed by NK cells and are immunogenetic determinants of the outcome of cancer. In particular, KIR2DS2 is associated with protective responses to several cancers and also direct recog...

Background The worldwide pandemic caused by SARS-CoV-2 has claimed millions of lives and has had a profound effect on global life. Understanding the pathogenicity of the virus and the body’s response to infection is crucial in improving patient management, prognosis, and therapeutic strategies. To address this, we performed functional transcriptomi...

The future of single cell diversity screens involves ever-larger sample sizes, dictating the need for higher throughput methods with low analytical noise to accurately describe the nature of the cellular system. Current approaches are limited by the Poisson statistic, requiring dilute cell suspensions and associated losses in throughput. In this co...

Background: One of the most severe forms of T cell mediated cutaneous adverse drug reactions is drug reaction with eosinophilia and systemic symptoms (DRESS), hence subsequent avoidance of the causal drug is imperative. However, attribution of drug culpability in DRESS is challenging and standard skin allergy tests are not recommended due to for pa...

Langerhans cells (LCs) reside in the epidermis as a dense network of immune system sentinels, coordinating both immunogenic and tolerogenic immune responses. To determine molecular switches directing induction of LC immune activation, we performed mathematical modelling of gene regulatory networks identified by single cell RNA sequencing of LCs exp...

Single-cell transcriptomics suffer from sensitivity limits that restrict low abundance transcript identification, affects clustering and can hamper downstream analyses. Here, we describe Constellation sequencing (Constellation-Seq), a molecular transcriptome filter that delivers two orders of magnitude sensitivity gains by maximising read utility w...

Background/Aims Crohn’s disease (CD) arises through host-environment interaction. Abnormal gene expression results from disturbed pathway activation or response to bacteria. We aimed to determine activated pathways and driving cell types in paediatric CD. Methods - We employed contemporary targeted autoimmune RNA sequencing, in parallel to single-...

BACKGROUND Tuberculosis (TB) kills more people than any other infection, and new diagnostic tests to identify active cases are required. We aimed to discover and verify novel markers for TB in nondepleted plasma.METHODS We applied an optimized quantitative proteomics discovery methodology based on multidimensional and orthogonal liquid chromatograp...

Background Atopic dermatitis (AD) arises from a complex interaction between an impaired epidermal barrier, environmental exposures, and the infiltration of Th1/Th2/Th17/Th22 T cells. Transcriptomic analysis has advanced understanding of gene expression in cells and tissues. However, molecular quantitation of cytokine transcripts does not predict th...

Natural killer (NK) cells are key components of the immune response to viral infections and cancer. Their functions are controlled by activating and inhibitory killer-cell immunoglobulin-like receptors (KIR) which have MHC class I ligands. KIR2DS2 is an activating KIR, that binds conserved viral peptides in the context of HLA-C and has been associa...

Langerhans cells (LC) can prime tolerogenic as well as immunogenic responses in skin, but the genomic states and transcription factors (TFs) regulating these context-specific responses are unclear. Bulk and single-cell transcriptional profiling demonstrates that human migratory LCs are robustly programmed for MHC-I and MHC-II antigen presentation....

Human epidermal Langerhans cells (LCs) can coordinate both immunogenic and tolerogenic immune responses, creating an attractive opportunity for immunomodulation strategies. To investigate transcriptional determinants of human primary LC tolerance we applied single cells RNA-sequencing combined with extensive functional analysis. Unsupervised cluste...

Background: Atopic dermatitis (AD) arises from a complex interaction between an impaired epidermal barrier, environmental exposures, and the infiltration of Th1/Th2/Th17/Th22 T cells. Transcriptomic analysis has advanced understanding of gene expression in cells and tissues. However, molecular quantitation of cytokine transcripts does not predict t...

Natural killer (NK) cells are innate immune cells that interface with the adaptive immune system to generate a pro-inflammatory immune environment. Primary Biliary Cholangitis (PBC) is a hepatic autoimmune disorder with extrahepatic associations including systemic sclerosis, Sjogren's syndrome and thyroiditis. Immunogenetic studies have identified...

Objectives: To dissect the transcriptional networks underpinning immune cells responses during primary Plasmodium vivax infection of healthy human adults. Methods: We conducted network co-expression analysis of next-generation RNA sequencing data from whole blood from P. vivax and P. falciparum controlled human malaria infection (CHMI) of health...

Langerhans cells (LCs) reside in the epidermis as a dense network of immune system sentinels. These cells determine the appropriate adaptive immune response (inflammation or tolerance) by interpreting the microenvironmental context in which they encounter foreign substances. In a normal physiological, “non-dangerous” situation, LCs coordinate a con...

Background The recent scale-up in malaria control measures in Latin America has resulted in a significant decrease in the number of reported cases in several countries including Ecuador, where it presented a low malaria incidence in recent years (558 reported cases in 2015) with occasional outbreaks of both Plasmodium falciparum and Plasmodium viva...

Background Reported urban malaria cases are increasing in Latin America, however, evidence of such trend remains insufficient. Here, we propose an integrated approach that allows characterizing malaria transmission at the rural-to-urban interface by combining epidemiological, entomological, and parasite genotyping methods. Methods/Principal findin...

Background Immunizing human volunteers by mosquito bite with radiation-attenuated Plasmodium falciparum sporozoites (RAS) results in high-level protection against infection. Only two volunteers have been similarly immunized with P. vivax (Pv) RAS, and both were protected. A phase 2 controlled clinical trial was conducted to assess the safety and pr...

Kaplan-Meier analysis of pre-patent and incubation period after P. vivax sporozoite CHMI. Days after CHMI to detect parasites by microscopy (A) or RT-qPCR (B) and onset of symptoms (C). (TIF)

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Antibody response against PvCS-N peptide and PvMSP-1. ELISA antibody response in RAS group (n = 12; A and C) and in Fy- group (n = 5; B and D) as well as in Ctl group (n = 2; red line in A to D) against PvCS-N (A-B) and PvMSP-1 (C-D) are shown. Values are expressed as reactivity index (RI) defined as sample OD at 1:200 serum dilutions divided by th...

Plasmodium vivax CS protein recognized by immunized volunteers. Western blot analysis of P. vivax sporozoites lysate separated on 12% SDS-PAGE under non-reducing conditions. Sera from RAS group (n = 12), Fy- group (n = 5), and Ctl group (n = 2) are shown. Negative (naïve volunteers) and positive (volunteers immunized with PvCSP) controls are also s...

Adverse events during immunizations and after CHMI. (XLS)

CONSORT checklist. (DOC)

Indirect immunofluorescence using Plasmodium vivax sporozoites. (DOC)

Additional methods. (DOC)

Clinical and laboratory exclusion criteria, assessment techniques and excluded volunteers. (DOC)

Screening of common infectious agents for recruited volunteers. (DOC)

Total number of mosquito bites received during immunizations. (XLSX)

Background Even though malaria incidence has decreased substantially in Guatemala since 2000, Guatemala remains one of the countries with the highest malaria transmission in Mesoamerica. Guatemala is committed to eliminating malaria as part of the initiative ‘Elimination of Malaria in Mesoamerica and the Island of Hispaniola’ (EMMIE); however, it i...

Leishmania infantum is one of the causative agents of visceral leishmaniasis (VL). VL is the most severe form of leishmaniasis and can be fatal if it is not properly treated. Although several PCR works are intended to detect L. infantum, in silico analysis of available primers and/or primer-probes reveals potential cross species amplification. Here...

Volunteer enrollment breakdown. (XLSX)

Cytokines correlation. (PNG)

Plasmodium vivax is a major public health burden, responsible for the majority of malaria infections outside Africa. We explored the impact of demographic history and selective pressures on the P. vivax genome by sequencing 182 clinical isolates sampled from 11 countries across the globe, using hybrid selection to overcome human DNA contamination....

Introduction: Individuals exposed to malaria infections for a long time develop immune responses capable of blocking Plasmodium transmission to mosquito vectors, potentially limiting parasite spreading in nature. Development of a malaria TB vaccine requires a better understanding of the mechanisms and main effectors responsible for transmission bl...

Background Plasmodium vivax 48/45 protein is expressed on the surface of gametocytes/gametes and plays a key role in gamete fusion during fertilization. This protein was recently expressed in Escherichia coli host as a recombinant product that was highly immunogenic in mice and monkeys and induced antibodies with high transmission-blocking activity...

Malaria control programmes rely on confirmation of parasite presence in patients’ blood prior to treatment administration. Plasmodium parasites are detected mostly by microscopy or rapid diagnostic test (RDT). Although these methods contribute significantly to malaria control/elimination, they are not suitable for detecting the significant proporti...

Background The use of molecular techniques has put in the spotlight the existence of a large mass of malaria sub-microscopic infections among apparently healthy populations. These sub-microscopic infections are considered an important pool for maintained malaria transmission. Methods In order to assess the appearance of Plasmodium vivax gametocytes...

Background: Multiplicity of infection (MOI) refers to the average number of distinct parasite genotypes concurrently infecting a patient. Although several studies have reported on MOI and the frequency of multiclonal infections in Plasmodium falciparum, there is limited data on Plasmodium vivax. Here, MOI and the frequency of multiclonal infection...

Studies reporting multiclonal infections in P. vivax and P. falciparum. (XLSX)

Genetic polymorphism found in P. vivax and P. falciparum samples. Fragment size ranges per locus, number of alleles per locus, and heterozygosity (He) per locus are shown. (DOCX)

Plasmodium vivax is a major public health burden, responsible for the majority of malaria infections outside Africa. We explored the impact of demographic history and selective pressures on the P. vivax genome by sequencing 182 clinical isolates sampled from 11 countries across the globe, using hybrid selection to overcome human DNA contamination....

Plasmodium vivax is the most prevalent malarial species in South America and exerts a substantial burden on the populations it affects. The control and eventual elimination of P. vivax are global health priorities. Genomic research contributes to this objective by improving our understanding of the biology of P. vivax and through the development of...

Patient summary information. (DOCX)

Electropherograms showing peak profiles for 18 polymorphic microsatellite loci. The y-axis corresponds to fluorescence intensity (arbitrary units) and the x-axis is the PCR product length in base pairs (bp). The amplitude of the each peak in base pairs (bp) is shown in boxes underneath the peaks. The range of allele sizes for these small datasets i...

Extreme diversity windows. 10kb windows with unusually high or low genetic diversity. Values for θw^ and π^ are ×10−3. The values in the “Start” column are the position of the start of the genomic window in kb. (XLSX)

Characterization of 18 polymorphic P. vivax microsatellite loci. Size ranges of PCR products (in base pairs) are given for six of the Colombian P. vivax isolates. Sal-I was used as a positive control. Fluorescent dyes (Hex and 6-FAM) were used to label forward primers only. ML: Motif length and No.A: allele numbers. (DOCX)

Methods used for microsatellite development. (DOCX)

Plasmodium vivax is the most prevalent malarial species in South America and exerts a substantial burden on the populations is affects. Its control and eventual elimination are a global health priority. Genomic research contributes to this objective by improving our understanding of the biology of P. vivax and through the development of new genetic...