Browsing by Subject "Innate immunity"

Now showing 1 - 7 of 7
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    Attachment of the soluble complement regulator factor H to cell and tissue surfaces: relevance for pathology
    (Murcia : F. Hernández, 2004) Józsi, M.; Manuelian, T.; Heinen, S.; Oppermann, M.; Zipfel, P.F.
    Complement is a central element of innate immunity and this vital defense system initiates and coordinates immediate immune reactions which attack and eliminate microbes, foreign particles and altered self cells. Newly generated activation products are extremely toxic and consequently, activation is highly restricted in terms of time and space. The initial activation of the alternative complement pathway occurs continuously and the early phase acts indiscriminatoryl and forms on any surface. However, the system discriminates between self and foreign, and therefore allows activation on foreign surfaces e.g. microbes, and restricts activation on host cells. Consequently, self cells and tissues are protected from the harmful activation products. This protection is mediated by specific regulators or inhibitors, which exist in the fluid phase and/or in membrane-bound forms. Here we review a novel mechanism, i.e. the attachment of the soluble complement regulator factor H to the surface of self cells. This attachment, which is demonstrated experimentally by means of immunofluorescense microscopy and by flow cytometry, increases the inhibitory potential at the cell surface and mediates protection by reducing the local formation of toxic inflammatory products. This attachment is highly relevant and has pathophysiological consequences in several human diseases, including Factor H-associated hemolytic uremic syndrome (FH-HUS), membranoproliferative glomerulonephritis type II, recurrent microbial infections and chronic inflammation, e.g. rheumatoid arthritis and immune evasion of tumor cells. Defects of this safeguard activity have been recently understood in patients with FH-HUS. Point mutations in the Factor H gene occurring in the C-terminus of the protein result in impaired cell binding capacity of Factor H and, consequently, during an inflammatory insult endothelial cells are not properly protected and are damaged.
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    Bottlenose dolphins (Tursiops truncatus) do also cast neutrophil extracellular traps against the apicomplexan parasite Neospora caninum
    (Elsevier, 2017-12) Villagra-Blanco, R.; Silva, L.M.R.; Aguilella-Segura, A.; Arcenillas Hernández, Irene; Martínez Carrasco-Pleite, Carlos; Seipp, A.; Gärtner, U.; Ruiz de Ybáñez Carnero, María del Rocío; Taubert, A.; Hermosilla, C.; Sanidad Animal
    Neutrophil extracellular traps (NETs) are web-like structures composed of nuclear DNA decorated with histones and cytoplasmic peptides which antiparasitic properties have not previously been investigated in cetaceans. Polymorphonuclear neutrophils (PMN) were isolated from healthy bottlenose dolphins (Tursiops truncatus), and stimulated with Neospora caninum tachyzoites and the NETs-agonist zymosan. In vitro interactions of PMN with the tachyzoites resulted in rapid extrusion of NETs. For the demonstration and quantification of cetacean NETs, extracellular DNA was stained by using either Sytox Orange® or Pico Green®. Scanning electron microscopy (SEM) and fluorescence analyses demonstrated PMN-derived release of NETs upon exposure to tachyzoites of N. caninum. Co-localization studies of N. caninum induced cetacean NETs proved the presence of DNA adorned with histones (H1, H2A/H2B, H3, H4), neutrophil elastase (NE), myeloperoxidase (MPO) and pentraxin (PTX) confirming the molecular properties of mammalian NETosis. Dolphin-derived N. caninum-NETosis were efficiently suppressed by DNase I and diphenyleneiodonium (DPI) treatments. Our results indicate that cetacean-derived NETs represent an ancient, conserved and relevant defense effector mechanism of the host innate immune system against N. caninum and probably other related neozoan parasites circulating in the marine environment.
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    Characterization of macrophages from the bony fish gilthead seabream using an antibody against the macrophage colony-stimulating factor receptor
    (Elsevier, 2008-04-07) Mulero Méndez, Iván; Sepulcre Cortés, María Pilar; Roca Soler, Francisco José; Meseguer Peñalver, J.; Garcia-Ayala, Alfonsa; Mulero Méndez, Victoriano Francisco; Bioquímica y Biología Molecular B e Inmunología
    Two major professional phagocyte populations have been described in fish, namely granulocytes and monocytes/macrophages. Although the distribution and localization of macrophages have been documented in several teleost species using mainly light and/or electron microscopy, the lack of appropriate markers for these cells has hampered our in-depth knowledge of their biology. We report here the generation of a monospecific rabbit polyclonal antibody against the gilthead seabream macrophage colony-stimulating factor receptor (Mcsfr), which is an excellent marker of macrophages in mammals and the zebrafish. The anti-Mcsfr has been found to be very useful in immunohistochemistry (IHC) to specifically immunostain the purified macrophages (adherent cells) obtained from the head-kidney as well as different cell populations in paraffin-embedded organs, including the head-kidney, spleen, thymus, gills and liver. Unexpectedly, however, no Mcsfr immunoreactive (Mcsfr+) cells were observed in the brain and intestine of the gilthead seabream. We also show that the distribution of Mcsfr+ cells in the head-kidney and the spleen is unaltered following infection with the fish pathogenic bacterium Vibrio anguillarum and that the Il1b-producing cells in these two organs after infection are exclusively acidophilic granulocytes. Finally, as the epitope recognized by the anti-Mcsfr is well conserved, we illustrate the potential usefulness of this antibody in other teleost species, such as the European seabass.
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    Erythrocyte phagocytosis in gilthead seabream (Sparus aurata) and European sea bass (Dicentrarchus labrax).
    (2024-11-04) Campos Sánchez, Jose Carlos; Guardiola, Francisco A.; Meseguer, José; Esteban Abad, María Ángeles; Biología celular e Histología
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    Isolation of functional mature peritoneal macrophages from healthy humans.
    (Wiley, 2019-11-06) Ruiz Alcaraz, Antonio José; Martínez Banaclocha, Helios; Marín Sánchez, Pilar; Carmona Martínez, Violeta; Iniesta Albadalejo, Miguel Ángel; Tristán Manzano, María; Tapia Abellán, Ana; García Peñarrubia, Pilar; Machado Linde, Francisco; Pelegrín, Pablo; Martínez Esparza, M.; Bioquímica y Biología Molecular B e Inmunología
    Macrophages play an important role in the inflammatory response. Their various biological functions are induced by different membrane receptors, including Toll-like receptors, which trigger several intracellular signaling cascades and activate the inflammasomes, which in turn elicit the release of inflammatory mediators such as cytokines. In this study, we present a novel method for the isolation of human mature peritoneal macrophages. This method can be easily implemented by gynecologists who routinely perform laparoscopy for sterilization by tubal ligation or surgically intervene in benign gynecological pathologies. Our method confirms that macrophages are the main peritoneal leukocyte subpopulation isolated from the human peritoneum in homeostasis. We showed that primary human peritoneal macrophages present phagocytic and oxidative activities, and respond to activation of the main proinflammatory pathways such as Toll-like receptors and inflammasomes, resulting in the secretion of different proinflammatory cytokines. Therefore, this method provides a useful tool for characterizing primary human macrophages as control cells for studies of molecular inflammatory pathways in steady-state conditions and for comparing them with those obtained from pathologies involving the peritoneal cavity. Furthermore, it will facilitate advances in the screening of anti-inflammatory compounds in the human system.
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    The bacterial mucosal immunotherapy MV130 protects against SARS-CoV-2 infection and improves COVID-19 vaccines immunogenicity
    (Frontiers Media, 2021-11-18) Fresno, Carlos del; García Arriaza, Juan; Martínez Cano, Sarai; Heras Murillo, Ignacio; Jarit Cabanillas, Aitor; Amores Iniesta, Joaquín; Brandy, Paola; Dunphy, Gillian; Suay Corredera, Carmen; Pricolo, María Rosaria; Vicente, Natalia; López Perrote, Andrés; Cabezudo, Sofía; González Corpas, Ana; Llorca, Oscar; Alegre Cebollada, Jorge; Garaigorfa, Urtzi; Gastaminza, Pablo; Esteban, Mariano; Sancho, David; Sanidad Animal
    COVID-19-specific vaccines are efficient prophylactic weapons against SARS-CoV-2 virus. However, boosting innate responses may represent an innovative way to immediately fight future emerging viral infections or boost vaccines. MV130 is a mucosal immunotherapy, based on a mixture of whole heat-inactivated bacteria, that has shown clinical efficacy against recurrent viral respiratory infections. Herein, we show that the prophylactic intranasal administration of this immunotherapy confers heterologous protection against SARS-CoV-2 infection in susceptible K18-hACE2 mice. Furthermore, in C57BL/6 mice, prophylactic administration of MV130 improves the immunogenicity of two different COVID-19 vaccine formulations targeting the SARS-CoV-2 spike (S) protein, inoculated either intramuscularly or intranasally. Independently of the vaccine candidate and vaccination route used, intranasal prophylaxis with MV130 boosted S-specific responses, including CD8+-T cell activation and the production of S-specific mucosal IgA antibodies. Therefore, the bacterial mucosal immunotherapy MV130 protects against SARS-CoV-2 infection and improves COVID-19 vaccines immunogenicity.
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    Toll like receptor-4 expression in lipopolysaccharide induced lung inflammation
    (Murcia : F. Hernández, 2006) Janardhan, K.; McIsaac, M.; Fowlie, J.; Shrivastav, A.; Caldwell, S.; Sharma, R.K.; Singh, B.
    Bacterial lipopolysaccharides (LPS) initiate immune response through Toll-like receptor 4 (TLR4). Because many a times host is confronted with secondary bacterial challenges, it is critical to understand TLR4 expression following initial provocation. We studied TLR4 expression in rats at various times after intratracheal instillation of LPS. Although TLR4 mRNA was undetectable in normal lungs, it increased at 6h and 12h and declined at 36h post-LPS treatment. Western blots showed TLR4 protein at all time points. Immunohistochemistry localized TLR4 in alveolar septal cells, bronchial epithelium, macrophages and endothelium of large and peribronchial blood vessels. Dual label immunoelectron microscopy showed colocalization of TLR4 and LPS in the cytoplasm and nucleus of various lung and inflammatory cells. Nuclear localization of TLR4 was confirmed with Western blots on lung nuclear extracts. We conclude that TLR4 expression in lung is sustained up to 36 hours and that TLR4 and LPS are localized in the cytoplasm and nuclei of lung cells