Candida albicans chitinase 3 with potential as a vaccine antigen: production, purification, and characterisation.

Chitinases are widely studied enzymes that have already found widespread application. Their continued development and valorisation will be driven by the identification of new and improved variants and/or novel applications bringing benefits to industry and society. We previously identified a novel application for chitinases wherein the Candida albicans cell wall surface chitinase 3 (Cht3) was shown to have potential in vaccine applications as a subunit antigen against fungal infections.

Interleukin-8 and Interleukin-6 Are Biomarkers of Poor Prognosis in Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a common type of cancer characterized by fast progression and high mortality rates, which generally implies a poor prognosis at time of diagnosis. Intricate interaction networks of cytokines produced by resident and inflammatory cells in the tumor microenvironment play crucial roles in ESCC development and metastasis, thus influencing therapy efficiency. As such, cytokines are the most prominent targets for specific therapies and prognostic parameters to predict tumor progression and aggressiveness.

Development of a Versatile Toolbox for Genetic Manipulation of .

has emerged as the most virulent species in the complex, accounting for sporotrichosis. Albeit the new insights into the understanding of host-pathogen interactions and comparative genomics of this fungi, the lack of genetic tools has hindered significant advances in this field of research. Here, we established an Agrobacterium tumefaciensmediated transformation (ATMT) system to transform different strains of .

Glutamine Metabolism Supports the Functional Activity of Immune Cells against Aspergillus fumigatus.

The reprogramming of cellular metabolism of immune cells is an essential process in the regulation of antifungal immune responses. In particular, glucose metabolism has been shown to be required for protective immunity against infection with Aspergillus fumigatus. However, given the intricate cross talk between multiple metabolic networks and signals, it is likely that cellular metabolic pathways other than glycolysis are also relevant during fungal infection.

Hypoxia inducible-factor 1 alpha regulates neutrophil recruitment during fungal-elicited granulomatous inflammation.

Chronic pulmonary aspergillosis (CPA) is a devastating disease with increasing prevalence worldwide. The characteristic granulomatous-like inflammation poses as the major setback to effective antifungal therapies by limiting drug access to fungi. These inflammatory lung structures are reported to be severely hypoxic; nevertheless, the underlying mechanisms whereby these processes contribute to fungal persistence remain largely unknown.

IL-10 Overexpression After BCG Vaccination Does Not Impair Control of Infection.

Control of tuberculosis depends on the rapid expression of protective CD4 T-cell responses in the (Mtb)-infected lungs. We have recently shown that the immunomodulatory cytokine IL-10 acts intrinsically in CD4 T cells and impairs their parenchymal migratory capacity, thereby preventing control of Mtb infection. Herein, we show that IL-10 overexpression does not impact the protection conferred by the established memory CD4 T-cell response, as BCG-vaccinated mice overexpressing IL-10 only during Mtb infection display an accelerated, BCG-induced, Ag85b-specific CD4 T-cell response and control Mtb infection.

Pentraxin 3 Inhibits Complement-driven Macrophage Activation to Restrain Granuloma Formation in Sarcoidosis.

Sarcoidosis is a multisystemic inflammatory disease characterized by the formation of granulomas in response to persistent stimuli. The long pentraxin PTX3 (pentraxin 3) has emerged as a component of humoral innate immunity with essential functions in the resolution of inflammation, but its role during granuloma formation is unknown. To evaluate PTX3 as a modulator of pathogenic signals involved in granuloma formation and inflammation in sarcoidosis.

Early IL-10 promotes vasculature-associated CD4+ T cells unable to control Mycobacterium tuberculosis infection.

Cytokine-producing CD4+ T cells play a crucial role in the control of Mycobacterium tuberculosis infection; however, there is a delayed appearance of effector T cells in the lungs following aerosol infection. The immunomodulatory cytokine IL-10 antagonizes control of M. tuberculosis infection through mechanisms associated with reduced CD4+ T cell responses.

Increased CD3, CD8, or FoxP3 T Lymphocyte Infiltrations Are Associated with the Pathogenesis of Colorectal Cancer but Not with the Overall Survival of Patients.

Tumor-infiltrating lymphocytes include heterogeneous populations of T lymphocytes that play crucial roles in the tumor immune response; importantly, their presence in the tumor tissue may predict clinical outcomes. Therefore, we herein studied the prognostic significance of the presence and location of CD3, CD8, and FoxP3 T lymphocytes in colorectal cancer samples. In the intratumor analysis, our data did not reveal any association between lymphocyte infiltrations with clinical or pathological data.

Immune System Efficiency in Cancer and the Microbiota Influence.

The immune system plays a critical role in preventing cancer development and progression. However, the complex network of cells and soluble factor that form the tumor microenvironment (TME) can dictate the differentiation of tumor-infiltrating leukocytes and shift the antitumor immune response into promoting tumor growth. With the advent of cancer immunotherapy, there has been a reinvigorated interest in defining how the TME shapes the antitumor immune response.

Changes in the Immune Phenotype and Gene Expression Profile Driven by a Novel Tuberculosis Nanovaccine: Short and Long-Term Post-immunization.

Deciphering protection mechanisms against () remains a critical challenge for the development of new vaccines and therapies. We analyze the phenotypic and transcriptomic profile in lung of a novel tuberculosis (TB) nanoparticle-based boosting mucosal vaccine Nano-FP1, which combined to BCG priming conferred enhanced protection in mice challenged with low-dose . We analyzed the vaccine profile and efficacy at short (2 weeks), medium (7 weeks) and long term (11 weeks) post-vaccination, and compared it to ineffective Nano-FP2 vaccine.

Phagosomal removal of fungal melanin reprograms macrophage metabolism to promote antifungal immunity.

In response to infection, macrophages adapt their metabolism rapidly to enhance glycolysis and fuel specialized antimicrobial effector functions. Here we show that fungal melanin is an essential molecule required for the metabolic rewiring of macrophages during infection with the fungal pathogen Aspergillus fumigatus. Using pharmacological and genetic tools, we reveal a molecular link between calcium sequestration by melanin inside the phagosome and induction of glycolysis required for efficient innate immune responses.

Glutamine supplementation improves the efficacy of miltefosine treatment for visceral leishmaniasis.

Background: The disturbance of host metabolic pathways by Leishmania parasites has crucial consequences for the activation status of immune cells and the outcome of infection. Glutamine has been described as an immunomodulatory amino acid, yet its role during Leishmania infection is still unknown.

Methods: We performed transcriptomics in uninfected and L.

The Absence of HIF-1α Increases Susceptibility to Leishmania donovani Infection via Activation of BNIP3/mTOR/SREBP-1c Axis.

Hypoxia-inducible factor-1 alpha (HIF-1α) is considered a global regulator of cellular metabolism and innate immune cell functions. Intracellular pathogens such as Leishmania have been reported to manipulate host cell metabolism. Herein, we demonstrate that myeloid cells from myeloid-restricted HIF-1α-deficient mice and individuals with loss-of-function HIF1A gene polymorphisms are more susceptible to L.

Myeloid HIF-1α regulates pulmonary inflammation during experimental Mycobacterium tuberculosis infection.

The transcription factor hypoxia-inducible factor-1 alpha (HIF-1α) is a key regulator of the response and function of myeloid cells in hypoxic and inflammatory microenvironments. To define the role of HIF-1α in tuberculosis, the progression of aerosol Mycobacterium tuberculosis infection was analysed in mice deficient in HIF-1α in the myeloid lineage (mHIF-1α ). We show that myeloid HIF-1α is not required for the containment of the infection, as both wild-type (WT) and mHIF-1α mice mounted normal Th1 responses and maintained control of bacterial growth throughout infection.

Antibacterial free-standing polysaccharide composite films inspired by the sea.

The adhesive capabilities of marine mussel proteins are well-known, exhibiting the ability to stick to different underwater substrates, either inorganic or organic. These unique adhesive properties are due to the high levels of amino acid, 3,4-dihydroxyphenyl-l-alanine (DOPA), which presents the reactive catechol group. Herein, novel antibacterial free-standing (FS) films were developed with natural polymers, namely chitosan (CHT) and hyaluronic acid (HA), being the catechol-functionalized hyaluronic acid (HA-DN) also included to provide wet adhesive properties.

Ploidy Determination in the Pathogenic Fungus spp.

The pathogenic clade of the genus comprises the etiological agents of sporotrichosis, a worldwide emergent disease. Despite the growing understanding of their successful pathogen traits, there is little information on genome sizes and ploidy within the genus. Therefore, in this work, we evaluated the ploidy of four species of the genus, specifically , , , and .

PTX3 Polymorphisms Influence Cytomegalovirus Reactivation After Stem-Cell Transplantation.

Reactivation of latent human cytomegalovirus (CMV) in patients undergoing allogeneic stem-cell transplantation (HSCT) predisposes to several clinical complications and is therefore a major cause of morbidity and mortality. Although pentraxin-3 (PTX3) has been previously described to bind both human and murine CMV and mediate several host antiviral mechanisms, whether genetic variation in the locus influences the risk of CMV infection is currently unknown. To dissect the contribution of genetic variation within to the development of CMV infection, we analyzed described loss-of-function variants at the locus in 394 recipients of HSCT and their corresponding donors and assessed the associated risk of CMV reactivation.

Metabolic Host Response to Intracellular Infections.

The interaction between intracellular bacterial pathogens with the host immune response can result in multiple outcomes that range from asymptomatic clearance to the establishment of infection. At its core, these interactions result in multiple metabolic adaptations of both the pathogen and its host cell. There is growing evidence that the host metabolic response plays a key role in the development of immune responses against the invading pathogen.

A Nonribosomal Peptide Synthase Gene Driving Virulence in Mycobacterium tuberculosis.

Nonribosomal peptide synthases produce short peptides in a manner that is distinct from classical mRNA-dependent ribosome-mediated translation. The genome harbors a nonribosomal peptide synthase gene, , which is part of a gene cluster proposed to be involved in the biosynthesis of isonitrile lipopeptides. Orthologous clusters are found in other slow-growing pathogenic mycobacteria and actinomycetes.

Exploring inhalable polymeric dry powders for anti-tuberculosis drug delivery.

The growing interest on polymeric delivery systems for pulmonary administration of drugs anticipates a more direct and efficient treatment of diseases such as tuberculosis (TB) that uses the pulmonary route as the natural route of infection. Polymeric microparticles or nano-in-microparticles offer target delivery of drugs to the lungs and the potential to control and sustain drug release within TB infected macrophages improving the efficiency of the anti-TB treatment and reducing side effects. In a dry powder form these inhalable delivery systems have increased stability and prolonged storage time without requiring refrigeration, besides being cost-effective and patient convenient.

L-Threonine Supplementation During Colitis Onset Delays Disease Recovery.

Dietary nutrients have emerged as potential therapeutic adjuncts for inflammatory bowel disease (IBD) given their impact on intestinal homeostasis through the modulation of immune response, gut microbiota composition and epithelial barrier stability. Several nutrients have already been associated with a protective phenotype. Yet, there is a lack of knowledge toward the most promising ones as well as the most adequate phase of action.

The impact of IL-10 dynamic modulation on host immune response against visceral leishmaniasis.

Leishmaniasis is a vector-borne disease caused by protozoan parasites from the genus Leishmania. The most severe form of disease is visceral leishmaniasis (VL), which is fatal if left untreated. It has been demonstrated that interleukin (IL)-10, is associated with disease progression and susceptibility.