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Book: Metabolic interaction in infection

Silvestre, Ricardo / Torrado, Egídio

(Experentia Supplementum ; 109)

2018

Author's details	Ricardo Silvestre, Egídio Torrado, editors
Series title	Experentia Supplementum ; 109 Experientia
Collection	Experientia
Language	English
Size	viii, 476 Seiten, Illustrationen
Publisher	Springer
Publishing place	Cham
Publishing country	Switzerland
Document type	Book
HBZ-ID	HT019663594
ISBN	978-3-319-74931-0 ; 9783319749327 ; 3-319-74931-5 ; 3319749323
Database	Catalogue ZB MED Medicine, Health

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Article ; Online: Immune System Efficiency in Cancer and the Microbiota Influence.

Barbosa, Ana Margarida / Gomes-Gonçalves, Alexandra / Castro, António G / Torrado, Egídio

Pathobiology : journal of immunopathology, molecular and cellular biology

2021 Volume 88, Issue 2, Page(s) 170–186

Abstract: 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 ...

Abstract	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. This interest brought to light the microbiome as a novel player in shaping cancer immunosurveillance. Indeed, accumulating evidence now suggests that the microbiome may confer susceptibility or resistance to certain cancers and may influence response to therapeutics, particularly immune checkpoint inhibitors. As we move forward into the age of precision medicine, it is vital that we define the factors that influence the interplay between the triad immune system-microbiota-cancer. This knowledge will contribute to improve the therapeutic response to current approaches and will unravel novel targets for immunotherapy.
MeSH term(s)	Animals ; Clinical Trials as Topic ; Disease Resistance ; Disease Susceptibility/microbiology ; Humans ; Immune System/pathology ; Immunotherapy/methods ; Mice ; Microbiota ; Neoplasms/immunology ; Neoplasms/pathology ; Neoplasms/therapy ; Precision Medicine ; Tumor Microenvironment
Language	English
Publishing date	2021-02-15
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	1022703-9
ISSN	1423-0291 ; 1015-2008
ISSN (online)	1423-0291
ISSN	1015-2008
DOI	10.1159/000512326
Database	MEDical Literature Analysis and Retrieval System OnLINE

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

Pastrez, Paula Roberta Aguiar / Barbosa, Ana Margarida / Mariano, Vânia Sammartino / Causin, Rhafaela Lima / Castro, Antonio Gil / Torrado, Egídio / Longatto-Filho, Adhemar

Cancers

2023 Volume 15, Issue 7

Abstract: 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 ... ...

Abstract	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. In this work, we examined the association between ESCC progression and the systemic levels of inflammatory cytokines to determine their usefulness as diagnostic biomarkers. We analyzed the levels of IL-1β, IL-6, IL-8, IL-10, TNF-α e IL-12p70 in a group of 70 ESCC patients and 70 healthy individuals using Cytometric Bead Array (CBA) technology. We detected increased levels of IL-1β, IL-6, IL-8, and IL-10 in ESCC patients compared to controls. However, multivariate analysis revealed that only IL8 was an independent prognostic factor for ESCC, as were the well-known risk factors: alcohol consumption, tobacco usage, and exposure to pesticides/insecticides. Importantly, patients with low IL-6, IL-8, TNM I/II, or those who underwent surgery had a significantly higher overall survival rate. We also studied cultured Kyse-30 and Kyse-410 cells in mice. We determined that the ESCC cell line Kyse-30 grew more aggressively than the Kyse-410 cell line. This enhanced growth was associated with the recruitment/accumulation of intratumoral polymorphonuclear leukocytes. In conclusion, our data suggest IL-8 as a valuable prognostic factor with potential as a biomarker for ESCC.
Language	English
Publishing date	2023-03-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15071997
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Article ; Online: Development of a Versatile Toolbox for Genetic Manipulation of

Tavares, Matheus / Sousa-Filho, Jorge Carlos / Machado, Ian Alves / Gonçales, Relber Aguiar / Antunes, Daniela / Mendes-Frias, Ana / Silvestre, Ricardo / Carvalho, Agostinho / Torrado, Egídio / Cunha, Cristina / Rodrigues, Fernando

Microbiology spectrum

2023 , Page(s) e0456422

Abstract: Sporothrix ... ...

Abstract	Sporothrix brasiliensis
Language	English
Publishing date	2023-02-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.04564-22
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Article ; Online: Candida albicans chitinase 3 with potential as a vaccine antigen: production, purification, and characterisation.

Costa-Barbosa, Augusto / Ferreira, Diogo / Pacheco, Maria Inês / Casal, Margarida / Duarte, Henrique Oliveira / Gomes, Catarina / Barbosa, Ana Margarida / Torrado, Egídio / Sampaio, Paula / Collins, Tony

Biotechnology journal

2023 Volume 19, Issue 1, Page(s) e2300219

Abstract: 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 ... ...

Abstract	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. In the present study, this enzyme was investigated further, developing production and purification protocols, enriching our understanding of its properties, and advancing its application potential. Cht3 was heterologously expressed in Pichia pastoris and a 4-step purification protocol developed and optimised: this involves activated carbon treatment, hydrophobic interaction chromatography, ammonium sulphate precipitation, and gel filtration chromatography. The recombinant enzyme was shown to be mainly O-glycosylated and to retain the epitopes of the native protein. Functional studies showed it to be highly specific, displaying activity on chitin, chitosan, and chito-oligosaccharides larger than chitotriose only. Furthermore, it was shown to be a stable enzyme, exhibiting activity, and stability over broad pH and temperature ranges. This study represents an important step forward in our understanding of Cht3 and contributes to its development for application.
MeSH term(s)	Candida albicans/genetics ; Candida albicans/metabolism ; Chitinases/genetics ; Chitinases/chemistry ; Proteins ; Chitin/chemistry ; Chitin/metabolism ; Chitosan ; Hydrogen-Ion Concentration
Chemical Substances	Chitinases (EC 3.2.1.14) ; Proteins ; Chitin (1398-61-4) ; Chitosan (9012-76-4)
Language	English
Publishing date	2023-10-30
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2221885-3
ISSN	1860-7314 ; 1860-6768
ISSN (online)	1860-7314
ISSN	1860-6768
DOI	10.1002/biot.202300219
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Article: Metabolic Host Response to Intracellular Infections.

Ferreira, Catarina M / Barbosa, Ana Margarida / Pereira, Inês M / Torrado, Egídio

Experientia supplementum (2012)

2018 Volume 109, Page(s) 319–350

Abstract: 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 ...

Abstract	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. However, successful intracellular pathogens have developed multiple mechanisms to circumvent the host response to thrive in the intracellular compartment. Here, we provide a brief overview on the crucial role of fundamental metabolic host responses in the generation of protective immunity to intracellular bacterial pathogens and discuss some of the mechanisms used by these pathogens to exploit the host metabolic response to their own advantage. This understanding will further our knowledge in host-pathogen interactions and may provide new insights for the development of novel therapies.
MeSH term(s)	Biochemical Phenomena ; Host-Pathogen Interactions ; Humans ; Immune System/metabolism ; Infection/metabolism
Language	English
Publishing date	2018-12-07
Publishing country	Switzerland
Document type	Journal Article
ISSN	1664-431X
ISSN	1664-431X
DOI	10.1007/978-3-319-74932-7_8
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Cytokines in the balance of protection and pathology during mycobacterial infections.

Torrado, Egídio / Cooper, Andrea M

Advances in experimental medicine and biology

2013 Volume 783, Page(s) 121–140

Abstract: The outcome of natural infections with pathogenic mycobacteria can range from early asymptomatic clearance through latent infection to clinical disease. Different host and pathogen-specific factors have been implicated in determining the outcome of these ...

Abstract	The outcome of natural infections with pathogenic mycobacteria can range from early asymptomatic clearance through latent infection to clinical disease. Different host and pathogen-specific factors have been implicated in determining the outcome of these infections; however, it is clear that the interaction of mycobacteria with the innate and acquired components of the immune system plays a central role. Specifically, the recognition of mycobacterial components by innate immune cells through different pathogen recognition receptors (PPRs) induces a cytokine response that can promote early control of the infection. In fact, in the majority of individuals that come into contact with mycobacteria, this response is enough to control the infection. Among PRRs, Toll-like receptors (TLRs), Nucleotide Oligomerization Domain (NOD)-like receptors, and C-type lectins have all been implicated in recognition of mycobacteria and in the initiation of the cytokine response. Defining the mechanisms by which distinct mycobacterial components and their receptors stimulate the immune response is an area of intense research.
MeSH term(s)	Cytokines/physiology ; Disease Susceptibility ; Eicosanoids/immunology ; Host-Pathogen Interactions/immunology ; Humans ; Immunity, Innate ; Interleukins/immunology ; Lectins, C-Type/immunology ; Macrophages/immunology ; Macrophages/microbiology ; Models, Immunological ; Mycobacterium Infections/immunology ; Mycobacterium Infections/microbiology ; Mycobacterium Infections/pathology ; Mycobacterium tuberculosis/immunology ; Nod Signaling Adaptor Proteins/immunology ; Phagocytosis ; T-Lymphocyte Subsets/immunology ; Toll-Like Receptors/immunology ; Tumor Necrosis Factor-alpha/immunology
Chemical Substances	Cytokines ; Eicosanoids ; Interleukins ; Lectins, C-Type ; Nod Signaling Adaptor Proteins ; Toll-Like Receptors ; Tumor Necrosis Factor-alpha
Language	English
Publishing date	2013-03-07
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2214-8019 ; 0065-2598
ISSN (online)	2214-8019
ISSN	0065-2598
DOI	10.1007/978-1-4614-6111-1_7
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Antibacterial free-standing polysaccharide composite films inspired by the sea.

Vale, A Catarina / Pereira, Paulo / Barbosa, A Margarida / Torrado, Egídio / Mano, João F / Alves, Natália M

International journal of biological macromolecules

2019 Volume 133, Page(s) 933–944

Abstract: 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- ... ...

Abstract	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. In order to obtain composite films, silver doped bioglass nanoparticles (Ag-BGs) were incorporated to promote bactericidal and bioactive properties, being tested four distinct formulations of FS films. Their surface morphology and topography, wettability, weight loss, swelling, mechanical, adhesion and bioactivity was analyzed. In particular, bioactivity tests revealed that upon immersion in simulated body fluid, there was the formation of a bone-like apatite layer. Moreover, upon 16 h in direct contact with Staphylococcus aureus and Escherichia coli cultures, these FS films exhibited a clear antibacterial effect. Therefore, such bioactive, antibacterial and adhesive free-standing films could potentially be used as temporary guided bone regeneration films, in particular to regenerate small bone defects and also periodontal tissues.
MeSH term(s)	Animals ; Anti-Bacterial Agents/chemistry ; Anti-Bacterial Agents/pharmacology ; Biomimetic Materials/chemistry ; Biomimetic Materials/pharmacology ; Bivalvia ; Ceramics/chemistry ; Nanoparticles/chemistry ; Polysaccharides/chemistry ; Polysaccharides/pharmacology ; Silver/chemistry ; Tensile Strength ; Wettability
Chemical Substances	Anti-Bacterial Agents ; Bioglass ; Polysaccharides ; Silver (3M4G523W1G)
Language	English
Publishing date	2019-04-16
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	282732-3
ISSN	1879-0003 ; 0141-8130
ISSN (online)	1879-0003
ISSN	0141-8130
DOI	10.1016/j.ijbiomac.2019.04.102
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Article ; Online: IL-10 Overexpression After BCG Vaccination Does Not Impair Control of

Ferreira, Catarina M / Micheli, Consuelo / Barreira-Silva, Palmira / Barbosa, Ana Margarida / Resende, Mariana / Vilanova, Manuel / Silvestre, Ricardo / Cunha, Cristina / Carvalho, Agostinho / Rodrigues, Fernando / Correia-Neves, Margarida / Castro, António Gil / Torrado, Egídio

Frontiers in immunology

2022 Volume 13, Page(s) 946181

Abstract: Control of tuberculosis depends on the rapid expression of protective ... ...

Abstract	Control of tuberculosis depends on the rapid expression of protective CD4
MeSH term(s)	Animals ; BCG Vaccine ; Interleukin-10 ; Mice ; Mycobacterium tuberculosis ; Tuberculosis/microbiology ; Tuberculosis/prevention & control ; Vaccination
Chemical Substances	BCG Vaccine ; Interleukin-10 (130068-27-8)
Language	English
Publishing date	2022-07-22
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.946181
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Article ; Online: Hypoxia inducible-factor 1 alpha regulates neutrophil recruitment during fungal-elicited granulomatous inflammation.

da Silva-Ferreira, Sara / Duarte-Oliveira, Cláudio / Antunes, Daniela / Barbosa-Matos, Catarina / Mendes-Frias, Ana / Torrado, Egídio / Costa, Sandra / Silvestre, Ricardo / Cunha, Cristina / Carvalho, Agostinho

Frontiers in cellular and infection microbiology

2022 Volume 12, Page(s) 1005839

Abstract: 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 ... ...

Abstract	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. Hypoxia-inducible factor 1 alpha (HIF-1α), besides being the major cellular response regulator to hypoxia, is a known central immune modulator. Here, we used a model of Aspergillus fumigatus airway infection in myeloid-restricted HIF-1α knock-out (mHif1α<sup>-/-</sup> ) mice to replicate the complex structures resembling fungal granulomas and evaluate the contribution of HIF-1α to antifungal immunity and disease development. We found that fungal-elicited granulomas in mHif1α<sup>-/-</sup> mice had significantly smaller areas, along with extensive hyphal growth and increased lung fungal burden. This phenotype was associated with defective neutrophil recruitment and an increased neutrophil death, therefore highlighting a central role for HIF-1α-mediated regulation of neutrophil function in the pathogenesis of chronic fungal infection. These results hold the promise of an improved capacity to manage the progression of chronic fungal disease and open new avenues for additional therapeutic targets and niches of intervention.
MeSH term(s)	Mice ; Animals ; Neutrophil Infiltration ; Antifungal Agents ; Aspergillosis ; Inflammation ; Hypoxia ; Granuloma
Chemical Substances	Antifungal Agents
Language	English
Publishing date	2022-10-06
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2619676-1
ISSN	2235-2988 ; 2235-2988
ISSN (online)	2235-2988
ISSN	2235-2988
DOI	10.3389/fcimb.2022.1005839
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