γδ T cell-mediated cytotoxicity against patient-derived healthy and cancer cervical organoids.

Cervical cancer is a leading cause of death among women globally, primarily driven by high-risk papillomaviruses. However, the effectiveness of chemotherapy is limited, underscoring the potential of personalized immunotherapies. Patient-derived organoids, which possess cellular heterogeneity, proper epithelial architecture and functionality, and long-term propagation capabilities offer a promising platform for developing viable strategies.

Identification of drug candidates targeting monocyte reprogramming in people living with HIV.

Introduction: People living with HIV (PLHIV) are characterized by functional reprogramming of innate immune cells even after long-term antiretroviral therapy (ART). In order to assess technical feasibility of omics technologies for application to larger cohorts, we compared multiple omics data layers.

Methods: Bulk and single-cell transcriptomics, flow cytometry, proteomics, chromatin landscape analysis by ATAC-seq as well as drug stimulation were performed in a small number of blood samples derived from PLHIV and healthy controls from the 200-HIV cohort study.

Cytoskeletal dynamics in parasites.

Cytoskeletal dynamics are essential for cellular homeostasis and development for both metazoans and protozoans. The function of cytoskeletal elements in protozoans can diverge from that of metazoan cells, with microtubules being more stable and actin filaments being more dynamic. This is particularly striking in protozoan parasites that evolved to enter metazoan cells.

Vaccine development against tuberculosis before and after Covid-19.

Coronavirus disease (Covid-19) has not only shaped awareness of the impact of infectious diseases on global health. It has also provided instructive lessons for better prevention strategies against new and current infectious diseases of major importance. Tuberculosis (TB) is a major current health threat caused by (Mtb) which has claimed more lives than any other pathogen over the last few centuries.

nymph saliva protein blocks host inflammation and complement-mediated killing of Lyme disease agent, .

Tick serine protease inhibitors (serpins) play crucial roles in tick feeding and pathogen transmission. We demonstrate that Ixodes scapularis (Ixs) nymph tick saliva serpin (S) 41 (IxsS41), secreted by Borrelia burgdorferi (Bb)-infected ticks at high abundance, is involved in regulating tick evasion of host innate immunity and promoting host colonization by Bb. Recombinant (r) proteins were expressed in Pichia pastoris, and substrate hydrolysis assays were used to determine.

Panton-Valentine leukocidin-induced neutrophil extracellular traps lack antimicrobial activity and are readily induced in patients with recurrent PVL + -Staphylococcus aureus infections.

Staphylococcus aureus strains that produce the toxin Panton-Valentine leukocidin (PVL-SA) frequently cause recurrent skin and soft tissue infections. PVL binds to and kills human neutrophils, resulting in the formation of neutrophil extracellular traps (NETs), but the pathomechanism has not been extensively studied. Furthermore, it is unclear why some individuals colonized with PVL-SA experience recurring infections whereas others are asymptomatic.

Tuberculosis prevention: current strategies and future directions.

Background: An estimated one fourth of the world's population is infected with Mycobacterium tuberculosis, and 5-10% of those infected develop tuberculosis in their lifetime. Preventing tuberculosis is one of the most underutilized but essential components of curtailing the tuberculosis epidemic. Moreover, current evidence illustrates that tuberculosis manifestations occur along a dynamic spectrum from infection to disease rather than a binary state as historically conceptualized.

Malaria: moving beyond the search for magic bullets.

Round table discussion on challenges and opportunities in malaria research with Elena Levashina, Dominique Soldati-Favre, Andrew Waters, Friedrich Frischknecht, and Julian Rayner.

Resistance to host antimicrobial peptides mediates resilience of gut commensals during infection and aging in .

Resilience to short-term perturbations, like inflammation, is a fundamental feature of microbiota, yet the underlying mechanisms of microbiota resilience are incompletely understood. Here, we show that , a major commensal, stably colonizes the fruit fly gut during infection and is resistant to antimicrobial peptides (AMPs). By transposon screening, we identified mutants sensitive to AMPs.

Myddosome clustering in IL-1 receptor signaling regulates the formation of an NF-kB activating signalosome.

IL-1 receptor (IL-1R) signaling can activate thresholded invariant outputs and proportional outputs that scale with the amount of stimulation. Both responses require the Myddosome, a multiprotein complex. The Myddosome is required for polyubiquitin chain formation and NF-kB signaling.

Infection pre-Ad26.COV2.S-vaccination primes greater class switching and reduced CXCR5 expression by SARS-CoV-2-specific memory B cells.

Neutralizing antibodies strongly correlate with protection for COVID-19 vaccines, but the corresponding memory B cells that form to protect against future infection are relatively understudied. Here we examine the effect of prior SARS-CoV-2 infection on the magnitude and phenotype of the memory B cell response to single dose Johnson and Johnson (Ad26.COV2.

Relevance of Host Cell Surface Glycan Structure for Cell Specificity of Influenza A Viruses.

Influenza A viruses (IAVs) initiate infection via binding of the viral hemagglutinin (HA) to sialylated glycans on host cells. HA's receptor specificity towards individual glycans is well studied and clearly critical for virus infection, but the contribution of the highly heterogeneous and complex glycocalyx to virus-cell adhesion remains elusive. Here, we use two complementary methods, glycan arrays and single-virus force spectroscopy (SVFS), to compare influenza virus receptor specificity with virus binding to live cells.

Calcitic Prisms of The Giant Seashell Pinna Nobilis Form Light Guide Arrays.

The shells of the Pinnidae family are based on a double layer of single-crystal-like calcitic prisms and inner aragonitic nacre, a structure known for its outstanding mechanical performance. However, on the posterior side, shells are missing the nacreous layer, which raises the question of whether there can be any functional role in giving up this mechanical performance. Here, it is demonstrated that the prismatic part of the Pinna nobilis shell exhibits unusual optical properties, whereby each prism acts as an individual optical fiber guiding the ambient light to the inner shell cavity by total internal reflection.

Delineating the Seasonality of Varicella and Its Association With Climate in the Tropical Country of Colombia.

Background: Varicella causes a major health burden in many low- to middle-income countries located in tropical regions. Because of the lack of surveillance data, however, the epidemiology of varicella in these regions remains uncharacterized. In this study, based on an extensive dataset of weekly varicella incidence in children ≤10 during 2011-2014 in 25 municipalities, we aimed to delineate the seasonality of varicella across the diverse tropical climates of Colombia.

Metformin Increases Cell Viability and Regulates Pro-Inflammatory Response to Mtb.

Introduction: Current TB treatment regimens are pathogen-directed and can be severely compromised by the development of drug resistance. Metformin has been proposed as an adjunctive therapy for TB, however relatively little is known about how metformin modulates the cellular interaction between Mtb and macrophages. We aimed to characterize how metformin modulates Mtb growth within macrophages.

Human GBP1 Is Involved in the Repair of Damaged Phagosomes/Endolysosomes.

Mouse guanylate-binding proteins (mGBPs) are recruited to various invasive pathogens, thereby conferring cell-autonomous immunity against these pathogens. However, whether and how human GBPs (hGBPs) target (Mtb) and (Lm) remains unclear. Here, we describe hGBPs association with intracellular Mtb and Lm, which was dependent on the ability of bacteria to induce disruption of phagosomal membranes.

Grandmother presence improved grandchild survival against childhood infections but not vaccination coverage in historical Finns.

Grandmother presence can improve the number and survival of their grandchildren, but what grandmothers protect against and how they achieve it remains poorly known. Before modern medical care, infections were leading causes of childhood mortality, alleviated from the nineteenth century onwards by vaccinations, among other things. Here, we combine two individual-based datasets on the genealogy, cause-specific mortality and vaccination status of eighteenth- and nineteenth-century Finns to investigate two questions.

Visualization of Myddosome Assembly in Live Cells.

The Myddosome is an oligomeric protein complex composed of MyD88 and members of IL-1 receptor-associated kinase (IRAK) family that transduce signals from Toll-like and IL-1 family receptors. The molecular dynamics of Myddosome formation and how the Myddosome organizes downstream signaling reactions provide insight into how TLR/IL-1Rs activate a decisive cellular response critical for the induction of inflammation. Supported lipid membranes formed on a continuous glass coverslip have been extensively used to study the molecular dynamics of receptor signaling.

Molecular and functional properties of human Plasmodium falciparum CSP C-terminus antibodies.

Human monoclonal antibodies (mAbs) against the central repeat and junction domain of Plasmodium falciparum circumsporozoite protein (PfCSP) have been studied extensively to guide malaria vaccine design compared to antibodies against the PfCSP C terminus. Here, we describe the molecular characteristics and protective potential of 73 germline and mutated human mAbs against the highly immunogenic PfCSP C-terminal domain. Two mAbs recognized linear epitopes in the C-terminal linker with sequence similarity to repeat and junction motifs, whereas all others targeted conformational epitopes in the α-thrombospondin repeat (α-TSR) domain.

Mycobacterium tuberculosis hijacks host TRIM21- and NCOA4-dependent ferritinophagy to enhance intracellular growth.

Ferritin, a key regulator of iron homeostasis in macrophages, has been reported to confer host defenses against Mycobacterium tuberculosis (Mtb) infection. Nuclear receptor coactivator 4 (NCOA4) was recently identified as a cargo receptor in ferritin degradation. Here, we show that Mtb infection enhanced NCOA4-mediated ferritin degradation in macrophages, which in turn increased the bioavailability of iron to intracellular Mtb and therefore promoted bacterial growth.

Glycosylated nanoparticle-based PfCSP vaccine confers long-lasting antibody responses and sterile protection in mouse malaria model.

The development of an effective and durable vaccine remains a central goal in the fight against malaria. Circumsporozoite protein (CSP) is the major surface protein of sporozoites and the target of the only licensed Plasmodium falciparum (Pf) malaria vaccine, RTS,S/AS01. However, vaccine efficacy is low and short-lived, highlighting the need for a second-generation vaccine with superior efficacy and durability.