PLOS Pathogens

A role for substance P in promoting neurogenic inflammation and pain has been described in sickle cell disease (SCD). However its origin and contribution to SCD pathophysiology remain unclear. We measured substance P level in plasma from 225 patients with SCD and observed the highest concentrations during acute chest syndrome (ACS). Therefore, we tested the hypothesis that substance P may induce ACS. In transgenic sickle mice, unlike control mice, intravenous injection of substance P caused leth...

BackgroundDengue virus (DENV) appears to manipulate several cellular metabolic pathways to permit its replication and immune evasion in the host. Here, we employed high-resolution mass spectrometry (HR-MS) to investigate the serum metabolomic landscape of clinical DENV infection. MethodsSerum specimens from primary dengue (n=11), secondary dengue (n=9) samples, and healthy controls (n=10) were used for untargeted and targeted metabolomic quantification on a Waters Xevo G2-XS QTof Mass Spectrome...

Newly emerging influenza virus strains pose a constant threat as they encounter a population lacking neutralizing antibodies against the new strain. However, cross-reactive non-neutralizing antibodies (nnABs) may be present and assist in mitigating disease symptoms via various effector mechanisms, including antibody-dependent cellular cytotoxicity (ADCC). Although nnABs to influenza virus have received more attention lately, little information is available on their age-related prevalence, steady...

The virulence of Plasmodium falciparum is closely linked to P. falciparum erythrocyte membrane protein 1 (PfEMP1), encoded by a diverse var gene family. PfEMP1 mediates parasite immune evasion and vascular adhesion of infected red blood cells, contributing to severe disease. While expression of group A or domain cassettes (DC8 and DC13)-containing var genes have been associated with severe malaria, comparisons between the severe malaria syndromes remain limited. Furthermore, interactions between...

A new H3N2 variant (named subclade K) possesses several key hemagglutinin substitutions and is circulating widely during the 2025-2026 influenza season. In this report, we completed experiments to determine if the 2025-2026 seasonal influenza vaccine elicits antibodies in humans that recognize this variant. We find that H3N2 subclade K viruses are antigenically advanced; however, the 2025-2026 seasonal influenza vaccine elicited antibodies in many individuals that efficiently recognized these vi...

We examined whether the recent emergence of influenza A(H3N2) subclade K, associated with an unusually early influenza season in the Northern hemisphere, was accompanied by a reduction in human population immunity. Using virus neutralisation assays on pre-epidemic human sera collected in May 2025, we found evidence of moderate antigenic drift. Further, vaccines used in the 2024/2025 season induced cross-neutralising immunity. These findings provide timely insight for interpreting recent influenz...

Clade 2.3.4.4b highly pathogenic avian influenza A(H5N1) viruses continue to expand geographically and across mammalian hosts, raising concern about pandemic potential. The degree and specificity of pre-existing immunity in humans are key determinants of this risk. We analyzed hemagglutinin (HA)-and neuraminidase (NA)-specific antibody responses in 300 sera collected from adults in New York City. While HA directed binding antibodies to clade 2.3.4.4b H5 were low and hemagglutination-inhibiting a...

Antibiotic resistance genes (ARGs) circulating among clinically relevant bacteria pose serious challenges to public health. Given the ancient and environmental bacterial origins of ARGs, a better understanding of the carriers of ARGs beyond the clinically most relevant species is urgently needed for more farsighted resistance monitoring and intervention measures. While the risks of emerging ARGs from environmental sources have been recognized, the identification bottlenecks stem from the limitat...

In nonsuppressible HIV viremia (NSV), individuals have persistently detectable viral load despite adherence to [≥]2 fully active antiretroviral drugs. NSV represents an area of clinical uncertainty and an opportunity to understand the mechanisms of HIV persistence. We performed in-depth virologic characterization to identify distinct NSV phenotypes. We categorized participants into those who had persistent viremia after antiretroviral therapy (ART) initiation (primary NSV) and those who had N...

An H3N2 variant, named subclade K, continues to circulate widely during the 2025-2026 influenza season. This virus possesses a hemagglutinin (HA) protein that has eleven substitutions relative to the HA of the Northern Hemisphere 2025-2026 H3N2 vaccine strain. Many of these substitutions are in epitopes in well-characterized HA antigenic sites. Despite this, interim vaccine effectiveness studies indicate that the 2025-2026 influenza vaccine provides moderate protection against H3N2 subclade K in...

Individuals with occupational exposure to swine may have disproportionate risk for zoonosis with swine influenza A virus (IAV). To evaluate human antibody responses, sera or plasma from swine veterinarians, swine farm employees, and the general population were tested by hemagglutination inhibition (HI) assays against representative swine and human seasonal influenza vaccine strains. HI data were analyzed by antigenic cartography to assess strain relationships, and reproduction number modeling to...

Understanding host susceptibility to Mycobacterium tuberculosis (Mtb) is critical for the development of new vaccines. Certain individuals "resist" becoming infected with Mtb despite intensive exposure; however, it is unknown whether there is a genetic basis for "resistance" to Mtb infection across populations. Here we conducted a genome-wide association study (GWAS) of resistance to Mtb infection by carefully characterizing exposure to TB patients among 4,058 close contacts in India, Brazil, an...

Influenza H3N2 subclade K (J.2.4.1) is a genetic branch of H3N2 with 11 mutations in hemagglutinin and currently represents the dominant circulating influenza strain. We evaluated antibody responses to H3N2 subclade K before and after influenza vaccination in 46 healthy individuals. Our data show that baseline antibody responses to two H3N2 subclade K variants were lower than to other H1N1 and H3N2 strains and that antibody responses following vaccination were also less robust to the H3N2 subcla...

Ebola virus disease (EVD) survivors often present with clinical sequelae after acute disease resolution, called post-Ebola syndrome (PES). Why some survivors develop these sequelae and others do not is poorly defined. Altered metabolism has been noted in acute EVD but not studied in PES. We identified differential expression of metabolites involved in multiple metabolic pathways in EVD survivors with PES. This included the tricarboxylic acid cycle, amino acid, nucleotide, and short chain fatty a...

Ethiopian cutaneous leishmaniasis (CL) shows remarkably heterogeneous clinical presentations, but the underlying immunopathological mechanisms driving this heterogeneity in disease presentation remains poorly understood. To characterise the local immune response in Ethiopian CL, we performed spatial transcriptomics on paired lesional and non-lesional skin punch biopsies from five Ethiopian CL patients. We used reference-free deconvolution, morphology-guided regional analyses, and immunohistochem...

Prioritising malaria vaccine targets requires understanding immunity to genetically and structurally diverse parasite antigens, influencing antibody measurements and durability. We measured total IgG levels to 25 Plasmodium falciparum antigens and assessed their association with protection and antigen features. Antibodies were quantified in two longitudinal cohorts of Papua New Guinean children (5-14 years; n=647) experiencing high or moderate transmission. Associations between antibody levels a...

ObjectivePost-thrombotic syndrome (PTS), a common complication of deep vein thrombosis, lacks objective diagnostic biomarkers and its molecular mechanisms remain poorly understood. This study aimed to identify plasma biomarkers and clarify pathways using integrated multi-omics and machine learning. MethodsProteomic and metabolomic profiling of 75 PTS patients and 75 controls was performed. Differential expression analysis, pathway enrichment, and protein-metabolite network analysis were conduct...

Staphylococcus aureus plays a central role in the exacerbation of atopic dermatitis (AD), but the population structure and pathogenic determinants of strains colonizing AD patients remain poorly understood. It is unclear whether these strains mirror those circulating in the general community or whether specific clonal lineages are selectively adapted to the AD skin microenvironment. Data addressing this question are scarce, particularly in Portugal. In this study, we investigated the molecular e...

BackgroundMycobacterium tuberculosis (Mtb) genomic epidemiology often relies on culturing patient sputum, a time and labor-intensive process. Hybrid capture approaches have been successfully used to enrich Mtb DNA from complex clinical samples, yet the accuracy of variant identification from captured samples has not been systematically evaluated. MethodsWe created artificial strain mixtures of two well-characterized Mtb isolates such that the minor strain comprised 0-50% of Mtb DNA and serially...

BK polyomavirus (BKPyV) is a major complication in kidney transplant recipients (KTR), for whom no specific antiviral therapy is available. Modulation of immunosuppressive therapy results in virus clearance in most KTR with BKPyV DNAemia (controllers), but a significant minority fail to clear the virus (non-controllers). Here, we adapt LIBRA-seq, which links antibody sequence data to antigen specificity, to intact viral capsids of the four BKPyV genotypes to study and compare BKPyV-specific B-ce...