Biology subjects

Lay, S.

Publications and source records attributed to Lay, S..

5 recordsLinked to original sources

bioRxiv2026

Early Immune Hypoactivation and Persistent Innate Reprogramming Characterize Chronic Chikungunya Disease

Chikungunya virus (CHIKV) infection causes acute febrile illness and debilitating arthralgia, with up to 40-80% of patients developing chronic chikungunya disease characterized by persistent arthralgia and fatigue lasting months to years. The immunological mechanisms underlying this transition remain poorly understood. We performed longitudinal immune profiling of CHIKV-infected patients stratified by clinical outcome. Single-cell RNA sequencing of peripheral blood mononuclear cells collected during acute infection and six months post-infection was combined with multiplex plasma cytokine and flow cytometric analysis. Patients who later developed chronic symptoms were characterized by early innate immune hypoactivation during acute infection, characterized by reduced monocyte and dendritic cell frequencies, lower circulating IFN-, IL-6 and IL-8, and reduced antigen-presentation and interferon-associated transcriptional programs. This was accompanied by diminished adaptive immune activation, including reduced IL-17 and IL-21 and lower HLA-DR expression across multiple T-cell subsets. Cell-cell communication analysis further indicated impaired acute monocyte-centered immune coordination in chronic progressors, whereas non-chronic patients displayed stronger monocyte-driven innate-to-adaptive signaling. By six months, chronic patients showed persistent innate remodeling, including increased non-classical monocytes, altered plasmacytoid dendritic cell and natural killer cell transcriptional programs, elevated CXCL10, reduced IL-6 and MMP8, and emergence of NK-centered predicted communication networks. Longitudinal transcriptomic analysis further identified divergent immune recovery trajectories, most prominently in non-classical monocytes and plasmacytoid dendritic cells. Together, these findings suggest that chronic chikungunya disease is associated with early innate immune hypoactivation followed by persistent innate immune remodeling, providing insight into immune mechanisms that may contribute to post-viral chronic inflammatory syndromes.

immunology↗

bioRxiv2022

First-in-human evaluation of cutaneous innate and adaptive immunomodulation by mosquito bites

Mosquito-borne viruses are a growing global threat. Initial viral inoculation occurs in the skin via the mosquito bite, eliciting immune responses that shape the establishment of infection and pathogenesis. We aimed to cutaneous innate and adaptive immune responses to mosquito bites in individuals from endemic areas. In this single-arm, cross-sectional interventional study, we enrolled 30 healthy adult participants aged 18 to 45 years of age from Cambodia between October 2020 and January 2021. We performed 3-mm skin biopsies at baseline as well as 30 minutes, 4 hours, and 48 hours after a controlled feeding by uninfected Aedes aegypti mosquitos. The primary endpoints were measurement of changes in early and late innate responses in bitten vs unbitten skin by gene expression profiling, immunophenotyping, and cytokine profiling. Results revealed induction of neutrophil degranulation and recruitment of skin-resident dendritic cells and M2-macrophages in bitten skin. As the immune reaction progressed over time, T cell priming and regulatory pathways were upregulated along with a shift to a Th2-driven response and CD8+ T cell activation. In accordance, participants bitten skin cells produced less pro-inflammatory cytokines when stimulated by Ae. aegypti salivary gland extract. No unexpected adverse events occurred, and one patient was lost to follow-up at Day 14. These results identify key immune genes, cell types, and pathways in the human response to mosquito bites that can be leveraged to develop novel therapeutics and vector-targeted vaccine candidates to arboviral diseases. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=132 SRC="FIGDIR/small/489145v2_ufig1.gif" ALT="Figure 1"> View larger version (77K): org.highwire.dtl.DTLVardef@1ba2eaaorg.highwire.dtl.DTLVardef@4d9dd6org.highwire.dtl.DTLVardef@1b54dc8org.highwire.dtl.DTLVardef@5a104_HPS_FORMAT_FIGEXP M_FIG Panel shows evolution of the human skin response to Aedes aegypti bites over time. C_FIG

immunology↗

bioRxiv2021

Robust and Functional Immunity up to 9 months after SARS-CoV-2 infection: a Southeast Asian longitudinal cohort

Assessing the duration of humoral and cellular immunity remains key to overcome the current SARS-CoV-2 pandemic, especially in understudied populations in least developed countries. Sixty-four Cambodian individuals with laboratory-confirmed infection with asymptomatic or mild/moderate clinical presentation were evaluated for humoral immune response to the viral spike protein and antibody effector functions during acute phase of infection and at 6-9 months follow-up. Antigen-specific B cells, CD4+ and CD8+ T cells were characterized, and T cells were interrogated for functionality at late convalescence. Anti-spike (S) antibody titers decreased over time, but effector functions mediated by S-specific antibodies remained stable. S- and nucleocapsid (N)-specific B cells could be detected in late convalescence in the activated memory B cell compartment and are mostly IgG+. CD4+ and CD8+ T cell immunity was maintained to S and membrane (M) protein. Asymptomatic infection resulted in decreased ADCC and frequency of SARS-CoV-2-specific CD4+ T cells at late convalescence. Whereas anti-S antibodies correlated with S-specific B cells, there was no correlation between T cell response and humoral immunity. Hence, all aspects of a protective immune response are maintained up to nine months after SARS-CoV-2 infection in the absence of re-infection. One sentence summaryFunctional immune memory to SARS-CoV-2, consisting of polyfunctional antibodies, memory B cells and memory T cells are maintained up to nine months in a South-East Asian cohort in the absence of re-infection.

immunology↗

bioRxiv2020

IDseq - An Open Source Cloud-based Pipeline and Analysis Service for Metagenomic Pathogen Detection and Monitoring

BackgroundMetagenomic next generation sequencing (mNGS) has enabled the rapid, unbiased detection and identification of microbes without pathogen-specific reagents, culturing, or a priori knowledge of the microbial landscape. mNGS data analysis requires a series of computationally intensive processing steps to accurately determine the microbial composition of a sample. Existing mNGS data analysis tools typically require bioinformatics expertise and access to local server-class hardware resources. For many research laboratories, this presents an obstacle, especially in resource limited environments. FindingsWe present IDseq, an open source cloud-based metagenomics pipeline and service for global pathogen detection and monitoring (https://idseq.net). The IDseq Portal accepts raw mNGS data, performs host and quality filtration steps, then executes an assembly-based alignment pipeline which results in the assignment of reads and contigs to taxonomic categories. The taxonomic relative abundances are reported and visualized in an easy-to-use web application to facilitate data interpretation and hypothesis generation. Furthermore, IDseq supports environmental background model generation and automatic internal spike-in control recognition, providing statistics which are critical for data interpretation. IDseq was designed with the specific intent of detecting novel pathogens. Here, we benchmark novel virus detection capability using both synthetically evolved viral sequences, and real-world samples, including IDseq analysis of a nasopharyngeal swab sample acquired and processed locally in Cambodia from a tourist from Wuhan, China, infected with the recently emergent SARS-CoV-2. ConclusionThe IDseq Portal reduces the barrier to entry for mNGS data analysis and enables bench scientists, clinicians, and bioinformaticians to gain insight from mNGS datasets for both known and novel pathogens.

bioinformatics↗

bioRxiv2020

Rapid metagenomic characterization of a case of imported COVID-19 in Cambodia

Rapid production and publication of pathogen genome sequences during emerging disease outbreaks provide crucial public health information. In resource-limited settings, especially near an outbreak epicenter, conventional deep sequencing or bioinformatics are often challenging. Here we successfully used metagenomic next generation sequencing on an iSeq100 Illumina platform paired with an open-source bioinformatics pipeline to quickly characterize Cambodias first case of COVID-2019.

microbiology↗