We report the humanization of glycosylation pathway in yeast Pichia pastoris to secrete a human glycoprotein with uniform complex N-glycosylation. The process involved eliminating endogenous pathways, while properly localizing five active eukaryotic proteins, including mannosidases I and II, N-acetylglucosaminyl transferases uridine 5'-diphosphate (UDP)-N-acetylglucosamine transporter. Targeted localization enzymes enabled generation synthetic vivo pathway, which produced N-glycan...

Optical coherence tomography angiography (OCTA) is a non-invasive imaging modality that can acquire high-resolution volumes of the retinal vasculature and aid diagnosis ocular, neurological cardiac diseases. Segmenting visible blood vessels common first step when extracting quantitative biomarkers from these images. Classical segmentation algorithms based on thresholding are strongly affected by image artifacts limited signal-to-noise ratio. The use modern, deep learning-based methods has...

Abstract The coincidence between infections with parasitic worms and the reduced prevalence of allergic disease in humans animal models has prompted search for helminth molecules antiallergic antiinflammatory potential. We report herein that filarial cystatin, a secreted protease inhibitor nematodes, suppresses Th2-related inflammation ensuing asthmatic murine model OVA-induced airway responsiveness. Treatment recombinant cystatin inhibited eosinophil recruitment, levels OVA-specific total...

Mast cells (MCs) are potent inflammatory that distributed throughout mucosal barrier tissues and respond rapidly to pathogenic stimuli. During helminth infections, MCs play an important role as late-stage effectors. However, it is currently unknown whether contribute the early innate events determine priming of adaptive immunity. MC-deficient mouse strains mice treated with MC stabilizing agent cromolyn sodium had dramatically reduced Th2 type 2 cytokine production harbored increased...

Differentiated T helper (Th) cell lineages are thought to emerge from alternative fate decisions. However, recent studies indicated that differentiated Th cells can adopt mixed phenotypes during secondary immunological challenges. Here we show natural primary immune responses against parasites generate bifunctional Th1 and Th2 hybrid co-express the lineage-specifying transcription factors T-bet GATA-3 co-produce cytokines. The integration of Th1-promoting interferon (IFN)-γ interleukin...

Parasitic nematodes are potent modulators of immune reactivity in mice and men. Intestinal live close contact with commensal gut bacteria, provoke biased Th2 responses upon infection, subsequently lead to changes physiology. We hypothesized that murine nematode infection is associated distinct the intestinal bacterial microbiota composition. here studied inflammatory following hookworm Heligmosomoides polygyrus bakeri applied cultural molecular techniques quantitatively assess ileum, cecum...

Parasitic worms alter their host's immune system to diminish the inflammatory responses directed against them, using very efficient immunomodulating molecules. We have previously shown that helminth immunomodulator cystatin (AvCystatin) profoundly reduces progression of diseases via modulation macrophages. Here we elucidate signaling events in macrophages triggered by AvCystatin. Labeled AvCystatin was predominantly taken up and subsequently induced phosphorylation mitogen-activated protein...

Abstract The resistance of inbred mice to nematode infections varies depending on the extent protective Th2 responses. Here, we compared two mouse lines differing in infection with enteric Heligmosomoides polygyrus bakeri despite similar instruction GATA-3+ T effector cells. Resistant BALB/c rapidly recruited high numbers cells gut within 1-week time frame required for larval development intestinal submucosa. C57BL/6 failed optimal control early fitness, mucosal response peaking after 2...

Parasitic nematodes typically modulate T-cell reactivity, primarily during the chronic phase of infection. We analyzed role CD4-positive (CD4+) T effector (T(eff)) cells and regulatory (T(reg)) derived from mice chronically infected with intestinal nematode Heligmosomoides polygyrus. Different CD4+ subsets were transferred into naïve recipients that subsequently H. Adoptive transfer conventional T(eff) conferred protection led to a significant decrease in worm burdens polygyrus-infected...

Abstract Immunomodulation is a common feature of chronic helminth infections and mainly attributed to the secretion bioactive molecules, which target modify host immune cells. In this study, we show that immunomodulator AvCystatin, cysteine protease inhibitor, induces novel regulatory macrophage (Mreg; AvCystatin-Mreg), sufficient mitigate major parameters allergic airway inflammation colitis in mice. A single adoptive transfer AvCystatin-Mreg before allergen challenge suppressed...

Intestinal parasitic nematodes live in intimate contact with the host microbiota. Changes microbiome composition during nematode infection affect immune control of parasites and shifts abundance bacterial groups have been linked to immunoregulatory potential nematodes. Here we asked if small intestinal parasite Heligmosomoides polygyrus produces factors antimicrobial activity, senses its microbial environment anti-nematode regulatory responses are altered mice devoid gut microbes. We found...

New treatment strategies for inflammatory bowel disease are needed and parasitic nematode infections or application of helminth components improve clinical experimental gut inflammation. We genetically modified the probiotic bacterium Escherichia coli Nissle 1917 to secrete powerful immunomodulator cystatin in gut. This was tested a murine colitis model on post-weaning intestinal inflammation pigs, an outbred with gastrointestinal system similar humans. Application transgenic significantly...

Codon pair deoptimization is an efficient virus attenuation strategy, but the mechanism that leads to unknown. The strategy involves synthetic recoding of viral genomes alters positions synonymous codons, thereby increasing number suboptimal codon pairs and CpG dinucleotides in recoded genomes. Here we identify molecular deoptimization-based by studying influenza A viruses. We show cause attenuation, whereas increase has no effect. Furthermore, reduce both mRNA stability translation...

Ascaris spp. undergo extensive migration within the body before establishing patent infections in small intestinal tract of humans and pigs. However, whether larval is critical for inducing efficient type 2 responses remains poorly understood. Therefore, we investigated systemic versus local adaptive immune along hepato-tracheal suum during primary, single conventionally raised Neither initial invasion gut tissue nor through liver resulted discernable Th2 cell responses. In contrast,...

Abstract Here, we show that Treg limit intestinal pathology during nematode infection and they control the onset magnitude of anti‐parasitic Th Th2 response. Using mice expressing diptheria toxin receptor under foxp3 locus, removed Foxp3 + early phase with Heligmosomoides polygyrus bakeri . Depletion in infected animals did not affect adult worm burden, but led to increased at site infection. Infected, depleted displayed higher frequencies activated CD4 T cells levels cytokines IL‐4 IL‐13....

Immunity to intestinal nematodes requires CD4⁺ Th2‐cell responses, including IL‐4 and IL‐13 production. Chronic infection with leads downregulation of these few functional T helper (Th) 2 cells are detected in secondary lymphoid organs the chronic phase or after abrogation infection. Here, we show a natural murine Heligmosomoides polygyrus that highly memory Th2 persist lamina propria addition peritoneal cavity (PC) While both tissue‐resident (T RM ) populations proliferate situ express...

Nematode infections, in particular gastrointestinal nematodes, are widespread and co-infections with other parasites pathogens frequently encountered humans animals. To decipher the immunological effects of a protozoan infection on anti-helminth immune response we studied co-infection enteric nematode Heligmosomoides polygyrus mice previously infected Toxoplasma gondii. Protective responses against nematodes dependent parasite-specific Th2 associated IL-4, IL-5, IL-13, IgE, IgG1 antibodies....

Abstract Soil-transmitted helminths (STH) are widespread, with Ascaris lumbricoides infecting millions globally. Malaria and STH co-infections common in co-endemic regions. Artemisinin derivatives (ARTs)—artesunate, artemether, dihydroartemisinin—are standard malaria treatments also known to influence the energy metabolism of parasites, tumors, immune cells. Herein, we explore potential ARTs ascariasis either by directly targeting larvae or indirectly modifying macrophage responses. suum...

Introduction While research on the gut-liver axis in non-communicable liver diseases has expanded exponentially, few studies have investigated liver-gut relationship context of gastrointestinal nematode infections. This study aimed to determine whether liver-draining lymph nodes (LLNs) contribute immune response against a strictly enteric infection. Methods We analyzed cellular and functional responses portal (PLN) celiac (CLN) following infection with small intestinal Heligmosomoides...

Summary Background Some helminth infections are negatively associated with the prevalence of allergic disorders, arguing for a modulation reactions by parasites, depending on worm species, intensity and phase infection type disease. Objective The aim this study was to analyse influence chronic gastrointestinal nematode Heligmosomoides polygyrus , in murine model airway disease atopic dermatitis (AD), respectively. Methods Mice were infected H. systemically sensitized allergen ovalbumin....

The roles of Th1 and Th17 responses as mediators host protection pathology in the intestine are subjects intense research. In this study, we investigated a model intestinal inflammation driven by intracellular apicomplexan parasite Eimeria falciformis. Although IFN-γ was predominant cytokine during E. falciformis infection wild-type mice, it found to be dispensable for defense development inflammation. falciformis-infected IFN-γR(-/-) IFN-γ(-/-) mice developed dramatically exacerbated body...

Background Gastrointestinal nematodes are currently being evaluated as a novel therapeutic in the treatment of chronic human inflammatory disorders, due to their unique ability induce immunoregulatory pathways hosts. In particular, administration ova from pig whipworm Trichuris suis (T. suis; TSO) has been proposed for allergic, and autoimmune disorders. Despite these advances, biological through which TSO therapy modulates host immune system context disease remain undefined. Methods We...