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Article ; Online: Infection with hypervirulent

Maceiras, Ana Raquel / Silvério, Diogo / Gonçalves, Rute / Cardoso, Marcos S / Saraiva, Margarida

2023 Volume 14, Page(s) 1211404

Abstract: Introduction: During infection, bone marrow (BM) hematopoiesis is reprogrammed toward myeloid cell production, a mechanism named emergency myelopoiesis. In addition to replenishing myeloid cells, emergency myelopoiesis has been linked to trained ... ...

Abstract	Introduction: During infection, bone marrow (BM) hematopoiesis is reprogrammed toward myeloid cell production, a mechanism named emergency myelopoiesis. In addition to replenishing myeloid cells, emergency myelopoiesis has been linked to trained immunity, a process that allows enhanced innate immune responses to secondary challenges. Although hematopoietic alterations during tuberculosis (TB) have been described and Methods: To further address this issue, we aerosol- infected C57BL/6 mice with high doses of the hypervirulent M. tuberculosis isolate HN878 and monitored alterations to the BM. This experimental model better resembles the human blood immune signature of TB. Results and discussion: We found increased frequencies of lineage
MeSH term(s)	Humans ; Animals ; Mice ; Mice, Inbred C57BL ; Mycobacterium tuberculosis ; Trained Immunity ; Myelopoiesis ; Monocytes
Language	English
Publishing date	2023-06-13
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.2023.1211404
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Article ; Online: CD5L as a promising biological therapeutic for treating sepsis.

Oliveira, Liliana / Silva, M Carolina / Gomes, Ana P / Santos, Rita F / Cardoso, Marcos S / Nóvoa, Ana / Luche, Hervé / Cavadas, Bruno / Amorim, Irina / Gärtner, Fátima / Malissen, Bernard / Mallo, Moisés / Carmo, Alexandre M

Nature communications

2024 Volume 15, Issue 1, Page(s) 4119

Abstract: Sepsis results from systemic, dysregulated inflammatory responses to infection, culminating in multiple organ failure. Here, we demonstrate the utility of CD5L for treating experimental sepsis caused by cecal ligation and puncture (CLP). We show that ... ...

Abstract	Sepsis results from systemic, dysregulated inflammatory responses to infection, culminating in multiple organ failure. Here, we demonstrate the utility of CD5L for treating experimental sepsis caused by cecal ligation and puncture (CLP). We show that CD5L's important features include its ability to enhance neutrophil recruitment and activation by increasing circulating levels of CXCL1, and to promote neutrophil phagocytosis. CD5L-deficient mice exhibit impaired neutrophil recruitment and compromised bacterial control, rendering them susceptible to attenuated CLP. CD5L
MeSH term(s)	Animals ; Sepsis/immunology ; Sepsis/drug therapy ; Mice, Inbred C57BL ; Mice ; Neutrophils/immunology ; Neutrophils/metabolism ; Mice, Knockout ; Phagocytosis ; Chemokine CXCL1/metabolism ; Chemokine CXCL1/genetics ; Disease Models, Animal ; Male ; Neutrophil Infiltration/drug effects ; Cecum/surgery ; Recombinant Proteins/therapeutic use ; Recombinant Proteins/administration & dosage ; Humans ; Pore Forming Cytotoxic Proteins/metabolism ; Ligation ; Lipopolysaccharides ; Shock, Septic/immunology
Language	English
Publishing date	2024-05-15
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-024-48360-8
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Article ; Online: Physical Interactions With Bacteria and Protozoan Parasites Establish the Scavenger Receptor SSC4D as a Broad-Spectrum Pattern Recognition Receptor.

Cardoso, Marcos S / Santos, Rita F / Almeida, Sarah / Sá, Mónica / Pérez-Cabezas, Begoña / Oliveira, Liliana / Tavares, Joana / Carmo, Alexandre M

Frontiers in immunology

2021 Volume 12, Page(s) 760770

Abstract: Since the pioneering discoveries, by the Nobel laureates Jules Hoffmann and Bruce Beutler, that Toll and Toll-like receptors can sense pathogenic microorganisms and initiate, in vertebrates and invertebrates, innate immune responses against microbial ... ...

Abstract	Since the pioneering discoveries, by the Nobel laureates Jules Hoffmann and Bruce Beutler, that Toll and Toll-like receptors can sense pathogenic microorganisms and initiate, in vertebrates and invertebrates, innate immune responses against microbial infections, many other families of pattern recognition receptors (PRRs) have been described. One of such receptor clusters is composed by, if not all, at least several members of the scavenger receptor cysteine-rich (SRCR) superfamily. Many SRCR proteins are plasma membrane receptors of immune cells; however, a small subset consists of secreted receptors that are therefore in circulation. We here describe the first characterization of biological and functional roles of the circulating human protein SSC4D, one of the least scrutinized members of the family. Within leukocyte populations, SSC4D was found to be expressed by monocytes/macrophages, neutrophils, and B cells, but its production was particularly evident in epithelial cells of several organs and tissues, namely, in the kidney, thyroid, lung, placenta, intestinal tract, and liver. Similar to other SRCR proteins, SSC4D shows the capacity of physically binding to different species of bacteria, and this opsonization can increase the phagocytic capacity of monocytes. Importantly, we have uncovered the capacity of SSC4D of binding to several protozoan parasites, a singular feature seldom described for PRRs in general and here demonstrated for the first time for an SRCR family member. Overall, our study is pioneer in assigning a PRR role to SSC4D.
MeSH term(s)	Animals ; Bacteria ; Bacterial Infections/immunology ; Cell Line ; Epithelial Cells/immunology ; Humans ; Leishmania ; Leukocytes/immunology ; Neospora ; Phagocytosis ; Plasmodium berghei ; Protozoan Infections/immunology ; Receptors, Pattern Recognition/chemistry ; Receptors, Pattern Recognition/genetics ; Receptors, Pattern Recognition/immunology ; Recombinant Proteins/immunology ; Scavenger Receptors, Class B/chemistry ; Scavenger Receptors, Class B/genetics ; Scavenger Receptors, Class B/immunology ; Trypanosoma brucei brucei
Chemical Substances	Receptors, Pattern Recognition ; Recombinant Proteins ; SSC4D protein, human ; Scavenger Receptors, Class B
Language	English
Publishing date	2021-12-24
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.2021.760770
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Article ; Online: TNF-Mediated Compensatory Immunity to

Resende, Mariana / Cardoso, Marcos S / Fróis-Martins, Ricardo / Borges, Margarida / Jordan, Michael B / Castro, António Gil / Appelberg, Rui

Journal of immunology (Baltimore, Md. : 1950)

2019 Volume 203, Issue 9, Page(s) 2451–2458

Abstract: Granuloma formation is a hallmark of several infectious diseases, including those caused ... ...

Abstract	Granuloma formation is a hallmark of several infectious diseases, including those caused by
MeSH term(s)	Animals ; CD4-Positive T-Lymphocytes/physiology ; Granuloma/etiology ; Interferon-gamma/physiology ; Macrophage Activation/immunology ; Mice ; Mice, Inbred C57BL ; Mycobacterium avium/immunology ; Signal Transduction ; Tumor Necrosis Factor-alpha/physiology
Chemical Substances	Tumor Necrosis Factor-alpha ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2019-09-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1801594
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Article ; Online: Myeloid HIF-1α regulates pulmonary inflammation during experimental Mycobacterium tuberculosis infection.

Resende, Mariana / Ferreira, Catarina M / Barbosa, Ana Margarida / Cardoso, Marcos S / Sousa, Jeremy / Saraiva, Margarida / Castro, António G / Appelberg, Rui / Torrado, Egídio

Immunology

2019 Volume 159, Issue 1, Page(s) 121–129

Abstract: 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 ... ...

Abstract	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
MeSH term(s)	Animals ; Bacterial Load ; Cells, Cultured ; Disease Models, Animal ; Disease Progression ; Host-Pathogen Interactions ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Lung/immunology ; Lung/metabolism ; Lung/microbiology ; Mice, Inbred C57BL ; Mice, Knockout ; Mycobacterium tuberculosis/growth & development ; Mycobacterium tuberculosis/immunology ; Myeloid Cells/immunology ; Myeloid Cells/metabolism ; Myeloid Cells/microbiology ; Pneumonia/genetics ; Pneumonia/immunology ; Pneumonia/metabolism ; Pneumonia/microbiology ; Signal Transduction ; Tuberculosis, Pulmonary/genetics ; Tuberculosis, Pulmonary/immunology ; Tuberculosis, Pulmonary/metabolism ; Tuberculosis, Pulmonary/microbiology
Chemical Substances	Hif1a protein, mouse ; Hypoxia-Inducible Factor 1, alpha Subunit
Language	English
Publishing date	2019-11-10
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	80124-0
ISSN	1365-2567 ; 0019-2805 ; 0953-4954
ISSN (online)	1365-2567
ISSN	0019-2805 ; 0953-4954
DOI	10.1111/imm.13131
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Article ; Online: Lack of the Transcription Factor Hypoxia-Inducible Factor 1α (HIF-1α) in Macrophages Accelerates the Necrosis of Mycobacterium avium-Induced Granulomas.

Cardoso, Marcos S / Silva, Tânia M / Resende, Mariana / Appelberg, Rui / Borges, Margarida

Infection and immunity

2015 Volume 83, Issue 9, Page(s) 3534–3544

Abstract: The establishment of mycobacterial infection is characterized by the formation of granulomas, which are well-organized aggregates of immune cells, namely, infected macrophages. The granuloma's main function is to constrain and prevent dissemination of ... ...

Abstract	The establishment of mycobacterial infection is characterized by the formation of granulomas, which are well-organized aggregates of immune cells, namely, infected macrophages. The granuloma's main function is to constrain and prevent dissemination of the mycobacteria while focusing the immune response to a limited area. In some cases these lesions can grow progressively into large granulomas which can undergo central necrosis, thereby leading to their caseation. Macrophages are the most abundant cells present in the granuloma and are known to adapt under hypoxic conditions in order to avoid cell death. Our laboratory has developed a granuloma necrosis model that mimics the human pathology of Mycobacterium tuberculosis, using C57BL/6 mice infected intravenously with a low dose of a highly virulent strain of Mycobacterium avium. In this work, a mouse strain deleted of the hypoxia inducible factor 1α (HIF-1α) under the Cre-lox system regulated by the lysozyme M gene promoter was used to determine the relevance of HIF-1α in the caseation of granulomas. The genetic ablation of HIF-1α in the myeloid lineage causes the earlier emergence of granuloma necrosis and clearly induces an impairment of the resistance against M. avium infection coincident with the emergence of necrosis. The data provide evidence that granulomas become hypoxic before undergoing necrosis through the analysis of vascularization and quantification of HIF-1α in a necrotizing mouse model. Our results show that interfering with macrophage adaptation to hypoxia, such as through HIF-1α inactivation, accelerates granuloma necrosis.
MeSH term(s)	Animals ; Disease Models, Animal ; Flow Cytometry ; Granuloma/pathology ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Immunohistochemistry ; In Situ Nick-End Labeling ; Macrophages/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mycobacterium Infections/metabolism ; Mycobacterium Infections/pathology ; Mycobacterium avium ; Necrosis/metabolism ; Necrosis/microbiology
Chemical Substances	Hif1a protein, mouse ; Hypoxia-Inducible Factor 1, alpha Subunit
Language	English
Publishing date	2015-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218698-6
ISSN	1098-5522 ; 0019-9567
ISSN (online)	1098-5522
ISSN	0019-9567
DOI	10.1128/IAI.00144-15
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Article ; Online: Targeted macrophages delivery of rifampicin-loaded lipid nanoparticles to improve tuberculosis treatment.

Vieira, Alexandre Cc / Magalhães, Joana / Rocha, Sónia / Cardoso, Marcos S / Santos, Susana G / Borges, Margarida / Pinheiro, Marina / Reis, Salette

Nanomedicine (London, England)

2017 Volume 12, Issue 24, Page(s) 2721–2736

Abstract: Aim: This work aims to develop a mannosylated nanostructured lipid carrier (NLC) loaded with rifampicin to improve tuberculosis treatment.: Materials & methods: An active targeting strategy was used and the nanoparticles were characterized. Effects ... ...

Abstract	Aim: This work aims to develop a mannosylated nanostructured lipid carrier (NLC) loaded with rifampicin to improve tuberculosis treatment. Materials & methods: An active targeting strategy was used and the nanoparticles were characterized. Effects on cell viability and the antimycobacterial activity of the nanoformulations were evaluated. Results: The nanoparticles developed exhibited a size of about 315 nm and polydispersity <0.2. The drug encapsulation efficiency was higher than 90% and its release was sensitive to pH. The mannosylated NLCs showed efficient uptake by bone marrow derived macrophages. Further, rifampicin-loaded mannosylated NLCs were more efficient in inducing a decrease of intracellular growth of mycobacteria. Conclusion: The NLCs developed can be used as a promising carrier for safer and efficient management of tuberculosis.
MeSH term(s)	Animals ; Antibiotics, Antitubercular/chemistry ; Antibiotics, Antitubercular/pharmacology ; Biological Transport ; Cell Survival ; Drug Carriers/chemistry ; Drug Liberation ; Female ; Humans ; Hydrogen-Ion Concentration ; Lipids/chemistry ; Macrophages/cytology ; Macrophages/drug effects ; Macrophages/microbiology ; Mannose/chemistry ; Mice, Inbred C57BL ; Mycobacterium avium/drug effects ; Mycobacterium avium/isolation & purification ; Nanoparticles/chemistry ; Particle Size ; Rifampin/chemistry ; Rifampin/pharmacology ; Surface Properties ; Tuberculosis, Pulmonary/drug therapy
Chemical Substances	Antibiotics, Antitubercular ; Drug Carriers ; Lipids ; Mannose (PHA4727WTP) ; Rifampin (VJT6J7R4TR)
Language	English
Publishing date	2017-11-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2277839-1
ISSN	1748-6963 ; 1743-5889
ISSN (online)	1748-6963
ISSN	1743-5889
DOI	10.2217/nnm-2017-0248
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Article ; Online: Innate IFN-γ-Producing Cells Developing in the Absence of IL-2 Receptor Common γ-Chain.

Resende, Mariana / Cardoso, Marcos S / Ribeiro, Ana R / Flórido, Manuela / Borges, Margarida / Castro, António Gil / Alves, Nuno L / Cooper, Andrea M / Appelberg, Rui

Journal of immunology (Baltimore, Md. : 1950)

2017 Volume 199, Issue 4, Page(s) 1429–1439

Abstract: IFN-γ is known to be predominantly produced by lymphoid cells such as certain subsets of T cells, NK cells, and other group 1 innate lymphoid cells. In this study, we used IFN-γ reporter mouse models to search for additional cells capable of secreting ... ...

Abstract	IFN-γ is known to be predominantly produced by lymphoid cells such as certain subsets of T cells, NK cells, and other group 1 innate lymphoid cells. In this study, we used IFN-γ reporter mouse models to search for additional cells capable of secreting this cytokine. We identified a novel and rare population of nonconventional IFN-γ-producing cells of hematopoietic origin that were characterized by the expression of Thy1.2 and the lack of lymphoid, myeloid, and NK lineage markers. The expression of IFN-γ by this population was higher in the liver and lower in the spleen. Furthermore, these cells were present in mice lacking both the
MeSH term(s)	Animals ; Antibodies, Monoclonal/administration & dosage ; DNA-Binding Proteins/deficiency ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/immunology ; Granuloma/immunology ; Granuloma/microbiology ; Hematopoietic Stem Cells/immunology ; Immunity, Innate ; Immunocompromised Host/immunology ; Interferon-gamma/biosynthesis ; Interferon-gamma/genetics ; Interferon-gamma/immunology ; Interleukin Receptor Common gamma Subunit/deficiency ; Interleukin Receptor Common gamma Subunit/genetics ; Interleukin Receptor Common gamma Subunit/immunology ; Killer Cells, Natural/immunology ; Leukocyte Common Antigens/genetics ; Leukocyte Common Antigens/immunology ; Liver/cytology ; Liver/immunology ; Liver/microbiology ; Macrophages/immunology ; Mice ; Mice, Inbred C57BL ; Mycobacterium avium/growth & development ; Mycobacterium avium/immunology ; Nitric Oxide Synthase Type II/biosynthesis ; Nitric Oxide Synthase Type II/genetics ; Nitric Oxide Synthase Type II/immunology ; Spleen/cytology ; Spleen/immunology ; Thy-1 Antigens/genetics ; Thy-1 Antigens/immunology
Chemical Substances	Antibodies, Monoclonal ; DNA-Binding Proteins ; Interleukin Receptor Common gamma Subunit ; Rag2 protein, mouse ; Thy-1 Antigens ; Interferon-gamma (82115-62-6) ; Nitric Oxide Synthase Type II (EC 1.14.13.39) ; Nos2 protein, mouse (EC 1.14.13.39) ; Leukocyte Common Antigens (EC 3.1.3.48) ; Ptprc protein, mouse (EC 3.1.3.48)
Language	English
Publishing date	2017-07-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1601701
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