• Klíčová slova
• PHAGOCYTOSIS *, VIRUSES *,
• MeSH
• fagocytóza * MeSH
• lidé MeSH
• viry * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Phagocytosis is a complex process by which cells within most organ systems remove pathogens and cell debris. Phagocytosis is usually followed by inflammatory pathway activation, which promotes pathogen elimination and inhibits pathogen growth. Delayed pathogen elimination is the first step in sepsis development and a key factor in sepsis resolution. Phagocytosis thus has an important role during sepsis and likely contributes to all of its clinical stages. However, only a few studies have specifically explored and characterized phagocytic activity during sepsis. Here, we describe the phagocytic processes that occur as part of the immune response preceding sepsis onset and identify the elements of phagocytosis that might constitute a predictive marker of sepsis outcomes. First, we detail the key features of phagocytosis, including the main receptors and signaling hallmarks associated with different phagocytic processes. We then discuss how the initial events of phagosome formation and cytoskeletal remodeling might be associated with known sepsis features, such as a cytokine-driven hyperinflammatory response and immunosuppression. Finally, we highlight the unresolved mechanisms of sepsis development and progression and the need for cross-disciplinary approaches to link the clinical complexity of the disease with basic cellular and molecular mechanisms.

• MeSH
• cytokiny imunologie   MeSH
• fagocytóza * MeSH
• imunosupresivní léčba * MeSH
• lidé MeSH
• sepse imunologie   patologie   MeSH
• signální transdukce imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• cytokiny MeSH

Mast cells (MCs) are long-lived immune cells widely distributed at mucosal surfaces and are among the first immune cell type that can get in contact with the external environment. This study aims to unravel the mechanisms of reciprocal influence between mucosal MCs and Candida albicans as commensal/opportunistic pathogen species in humans. Stimulation of bone marrow-derived mast cells (BMMCs) with live forms of C. albicans induced the release of TNF-α, IL-6, IL-13, and IL-4. Quite interestingly, BMMCs were able to engulf C. albicans hyphae, rearranging their α-tubulin cytoskeleton and accumulating LAMP1+ vesicles at the phagocytic synapse with the fungus. Candida-infected MCs increased macrophage crawling ability and promoted their chemotaxis against the infection. On the other side, resting MCs inhibited macrophage phagocytosis of C. albicans in a contact-dependent manner. Taken together, these results indicate that MCs play a key role in the maintenance of the equilibrium between the host and the commensal fungus C. albicans, limiting pathological fungal growth and modulating the response of resident macrophages during infections.

• Klíčová slova
• candida, macrophages, mast cells, microbiota, phagocytosis,
• MeSH
• Candida albicans imunologie   MeSH
• cytokiny imunologie   MeSH
• fagocytóza * MeSH
• kandidóza imunologie   patologie   MeSH
• makrofágy imunologie   fyziologie   MeSH
• mastocyty imunologie   patologie   MeSH
• membránové glykoproteiny asociované s lyzozomy imunologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytokiny MeSH
• Lamp1 protein, mouse MeSH Prohlížeč
• membránové glykoproteiny asociované s lyzozomy MeSH

Immunotherapy emerges as a fundamental approach in cancer treatment. Up to date, the efficacy of numerous different immunotherapies has been evaluated. The use of microorganisms or their parts for immune cell activation, referred to as Pathogen-Associated Molecular Patterns (PAMPs), represents highly promising concept. The therapeutic effect of PAMPs can be further amplified by suitable combination of different types of PAMPs such as Toll like receptor (TLR) agonists and phagocytosis activating ligands. Previously, we used the combination of phagocytosis activating ligand (mannan) and mixture of TLR agonists (resiquimod (R-848), poly(I:C), inactivated Listeria monocytogenes) for successful treatment of melanoma in murine B16-F10 model. In the present study, we optimized the composition and timing of previously used mixture. Therapeutic mixture based on well-defined chemical compounds consisted of mannan anchoring to tumor cell surface by biocompatible anchor for membranes (BAM) and TLR agonists resiquimod, poly(I:C), and lipoteichoic acid (LTA). The optimization resulted in (1) eradication of advanced stage progressive melanoma in 83% of mice, (2) acquisition of resistance to tumor re-transplantation, and (3) potential anti-metastatic effect. After further investigation of mechanisms, underlying anti-tumor responses, we concluded that both innate and adaptive immunity are activated and involved in these processes. We tested the efficacy of our treatment in Panc02 murine model of aggressive pancreatic tumor as well. Simultaneous application of agonistic anti-CD40 antibody was necessary to achieve effective therapeutic response (80% recovery) in this model. Our results suggest that herein presented immunotherapeutic approach is a promising cancer treatment strategy with the ability to eradicate not only primary tumors but also metastases.

• Klíčová slova
• Cancer immunotherapy, Melanoma B16-F10, Metastasis, Panc02, Phagocytosis, TLR agonists,
• MeSH
• adenokarcinom imunologie   patologie   terapie   MeSH
• fagocytóza * MeSH
• imidazoly terapeutické užití   MeSH
• imunoterapie MeSH
• kyseliny teichoové terapeutické užití   MeSH
• lipopolysacharidy terapeutické užití   MeSH
• mannany terapeutické užití   MeSH
• melanom experimentální imunologie   patologie   terapie   MeSH
• myši inbrední C57BL MeSH
• nádorové buněčné linie MeSH
• nádory slinivky břišní imunologie   patologie   terapie   MeSH
• neutrofily imunologie   MeSH
• poly I-C terapeutické užití   MeSH
• toll-like receptory agonisté   MeSH
• tumor burden účinky léků   MeSH
• tumor infiltrující lymfocyty imunologie   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• imidazoly MeSH
• kyseliny teichoové MeSH
• lipopolysacharidy MeSH
• lipoteichoic acid MeSH Prohlížeč
• mannany MeSH
• poly I-C MeSH
• resiquimod MeSH Prohlížeč
• toll-like receptory MeSH

• Klíčová slova
• PHAGOCYTOSIS *,
• MeSH
• fagocytóza * MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The present concept of the transmission of Lyme disease from Borrelia-infected Ixodes sp. ticks to the naïve host assumes that a low number of spirochetes that manage to penetrate the midgut epithelium migrate through the hemocoel to the salivary glands and subsequently infect the host with the aid of immunomodulatory compounds present in tick saliva. Therefore, humoral and/or cellular immune reactions within the tick hemocoel may play an important role in tick competence to act as a vector for borreliosis. To test this hypothesis we have examined complement-like reactions in the hemolymph of the hard tick Ixodes ricinus against Borrelia afzelii (the most common vector and causative agent of Lyme disease in Europe). We demonstrate that I. ricinus hemolymph does not exhibit borreliacidal effects comparable to complement-mediated lysis of bovine sera. However, after injection of B. afzelii into the tick hemocoel, the spirochetes were efficiently phagocytosed by tick hemocytes and this cellular defense was completely eliminated by pre-injection of latex beads. As tick thioester-containing proteins (T-TEPs) are components of the tick complement system, we performed RNAi-mediated silencing of all nine genes encoding individual T-TEPs followed by in vitro phagocytosis assays. Silencing of two molecules related to the C3 complement component (IrC3-2 and IrC3-3) significantly suppressed phagocytosis of B. afzelii, while knockdown of IrTep (insect type TEP) led to its stimulation. However, RNAi-mediated silencing of T-TEPs or elimination of phagocytosis by injection of latex beads in B. afzelii-infected I. ricinus nymphs had no obvious impact on the transmission of spirochetes to naïve mice, as determined by B. afzelii infection of murine tissues following tick infestation. This result supports the concept that Borrelia spirochetes are capable of avoiding complement-related reactions within the hemocoel of ticks competent to transmit Lyme disease.

• Klíčová slova
• Borrelia, Ixodes, complement, phagocytosis, thioester-containing proteins,
• MeSH
• arachnida jako vektory imunologie   mikrobiologie   MeSH
• Borrelia burgdorferi komplex imunologie   MeSH
• fagocytóza * MeSH
• hemocyty imunologie   MeSH
• klíště imunologie   mikrobiologie   MeSH
• komplement metabolismus   MeSH
• lymeská nemoc přenos   MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• přenos infekční nemoci MeSH
• proteiny členovců metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• komplement MeSH
• proteiny členovců MeSH

• Klíčová slova
• ADNEXITIS/immunology *, PHAGOCYTOSIS *, VACCINATION *,
• MeSH
• fagocytóza * MeSH
• lidé MeSH
• pánevní zánět imunologie   MeSH
• vakcinace * MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Modafinil is a psychostimulant drug prescribed mainly for treatment of narcolepsy but is used as a "smart drug" by wide populations to increase wakefulness, concentration and overall mental performance. The aim of this study was to assess potential developmental toxicity of modafinil. MATERIALS AND METHODS: Pregnant female mice were given either saline or modafinil (50 mg/kg orally) from gestational day (GD) 3 to GD 10 and then a challenge dose on the GD 17. The male offspring were treated analogously at the age of 10 weeks. Changes in the spontaneous locomotor/exploratory behaviour and anxiogenic profile in the open-field test were assessed in naive animals, after an acute and 8th modafinil dose and the challenge dose following a 7-day wash-out period. One month after completion of the behavioural study, the leukocyte phagocytosis was examined by zymosan induced and luminol-aided chemiluminiscence assay in vitro. RESULTS: The most important finding of this study was the immunosuppressing effect on leukocyte activity, hypolocomotion and increased behavioural response to modafinil-induced psychostimulation caused by prenatal exposure to the same drug. We did not detect significantly altered anxiety-related behaviour in any group disregarding the pre- and postnatal treatments. CONCLUSION: This is the first evidence of developmental toxicity of modafinil which needs to be taken into account as a potential risk factor when modafinil is administered to women who may become or are pregnant.

• MeSH
• fagocytóza účinky léků   MeSH
• gestační stáří MeSH
• leukocyty účinky léků   MeSH
• lokomoce účinky léků   MeSH
• luminiscenční měření MeSH
• luminol MeSH
• modafinil škodlivé účinky   MeSH
• modely nemocí na zvířatech * MeSH
• myši inbrední ICR MeSH
• myši MeSH
• těhotenství MeSH
• věkové faktory MeSH
• zpožděný efekt prenatální expozice * MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• myši MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• luminol MeSH
• modafinil MeSH

The ability of ticks to act as vectors for a wide range of serious human and animal infectious diseases is apparently linked to the insufficiency of the tick immune system to effectively eliminate pathogens they transmit. At the tick-pathogen interface, an important role is presumably played by components of an ancient complement system that includes a repertoire of thioester-containing proteins (TEPs), which in Ixodes sp. comprises three α2-macroglobulins (A2M), three C3 complement component-related molecules (C3), two macroglobulin complement-related (Mcr) and one insect-type TEPs (Tep). In order to assess the function of TEPs in tick immunity, a quantitative real-time PCR expression analysis of tick TEPs was performed at various developmental stages of Ixodes ricinus, and in tissues dissected from adult females. Expression of TEP genes was mostly tissue specific; IrA2M1, IrC3-1, IrC3-3 were found to be expressed in cells of tick fat body adjacent to the tracheal trunks, IrA2M2 in hemocytes, IrTep in ovaries, IrMcr1 in salivary glands and only IrA2M3, IrC3-2 and IrMcr2 mRNAs were present in multiple organs. Expression of tick TEPs was further examined in response to injection of model microbes representing Gram-negative, Gram-positive bacteria and yeast. The greatest expression induction was observed for IrA2M1 and IrC3-1 after challenge with the yeast Candida albicans. Phagocytosis of the yeast was strongly dependent on an active thioester bond and the subsequent silencing of individual tick TEPs by RNA interference demonstrated the involvement of IrC3-1 and IrMcr2. This result suggests the existence of a distinct complement-like pathway, different from that leading to phagocytosis of Gram-negative bacteria. Understanding of the tick immune response against model microbes should provide new concepts for investigating interactions between ticks and relevant tick-borne pathogens.

• Klíčová slova
• Candida albicans, Complement, Innate immunity, Phagocytosis, Thioester-containing proteins, Tick Ixodes ricinus,
• MeSH
• Candida albicans imunologie   MeSH
• fagocytóza imunologie   MeSH
• gramnegativní bakterie imunologie   MeSH
• grampozitivní bakterie imunologie   MeSH
• hemolymfa imunologie   MeSH
• klíště genetika   imunologie   MeSH
• malá interferující RNA MeSH
• proteiny členovců biosyntéza   genetika   imunologie   MeSH
• RNA interference MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• malá interferující RNA MeSH
• proteiny členovců MeSH

A micromethod for testing of phagocytosis employing synthetic hydrophilic HEMA particles seems to be suitable for an examination of rat neutrophils. The normal phagocytic activity was 53.7 +/- 1.4%, phagocytic index 8.2 +/- 0.7, and the number of phagocytosing neutrophils was found to be 74 +/- 5.10(6)/l. Using HEMA particles, an experimentally induced depression of rat neutrophil phagocytosis after cyclophosphamide or benflurone was well detected and quantified.

• MeSH
• cyklofosfamid farmakologie   MeSH
• fagocytóza * účinky léků   MeSH
• fluoreny farmakologie   MeSH
• inbrední kmeny potkanů MeSH
• krysa rodu Rattus MeSH
• kyseliny polymethakrylové * MeSH
• neutrofily fyziologie   MeSH
• polyhydroxyethylmethakrylát * MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• cyklofosfamid MeSH
• fluoreny MeSH
• kyseliny polymethakrylové * MeSH
• polyhydroxyethylmethakrylát * MeSH
• VUFB 13468 MeSH Prohlížeč