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.
- 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
Ticks possess components of a primordial complement system that presumably play a role in the interaction of the tick immune system with tick-borne pathogens and affect their transmission. Here we characterized a novel complement component, tagged as IrC2/Bf, from the hard tick Ixodes ricinus, the principal vector of Lyme disease in Europe. IrC2/Bf is a multi-domain molecule composed of 5-7 CCP modules, varied by alternative splicing, followed by a von Willebrand factor A domain and a C-terminal trypsin-like domain. The primary structure and molecular architecture of IrC2/Bf displays the closest homology to the C3-complement component convertases described in horseshoe crabs. The irc2/bf gene is mainly expressed in the tick fat body associated with the trachea and, as determined by western blotting, the protein is present in low amounts in tick hemolymph. Expression of irc2/bf mRNA was significantly up-regulated in response to the intra-hemocoelic injection of the yeast Candida albicans and all tested Borrelia sp. strains (B. burgdorferi NE5264, B. burgdorferi CB26, B. garinii MSLB, B. afzelii CB43), but was not affected by injection of model Gram-negative and Gram-positive bacteria or the aseptic injection control. In-line with these results, RNAi-mediated silencing of irc2/bf inhibited phagocytosis of B. afzelii and C. albicans but not the other bacteria. Tissue expression profiles, specific responses to microbial challenges, and patterns of phagocytic phenotypes upon RNAi silencing observed for IrC2/Bf match well with the previously reported characteristics of I. ricinus C3-related molecule 1 (IrC3-1). Therefore we presume that IrC2/Bf functions as a convertase in the same complement activation pathway protecting ticks against yeast and Borrelia infection.
- MeSH
- aktivace komplementu MeSH
- Borrelia burgdorferi imunologie MeSH
- Candida albicans imunologie MeSH
- fagocytóza MeSH
- hemocyty imunologie mikrobiologie MeSH
- hmyzí proteiny genetika metabolismus MeSH
- infekce přenášené vektorem MeSH
- interakce hostitele a patogenu MeSH
- kandidóza imunologie MeSH
- klíště imunologie MeSH
- komplement C3 genetika metabolismus MeSH
- lidé MeSH
- lymeská nemoc imunologie MeSH
- malá interferující RNA genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem 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.
- 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
Due to the growing incidence of systemic and superficial candida infections, targeted laboratory diagnostic methods are investigated. The available serologic and microbiological methods are summarized. The pros and cons of relevant serologic methods with respect to their sensitivity to and specificity of candida antigens or anti-candida antibodies are stressed.
- Klíčová slova
- diagnostika in vitro,
- MeSH
- buněčná stěna chemie imunologie MeSH
- Candida albicans * chemie imunologie MeSH
- imunochemie metody MeSH
- kandidóza * diagnóza imunologie patofyziologie MeSH
- klinické laboratorní techniky * metody využití MeSH
- lidé MeSH
- molekulární struktura MeSH
- odběr biologického vzorku MeSH
- polysacharidy * analýza chemie imunologie MeSH
- sérologické testy MeSH
- Check Tag
- lidé MeSH
Limulus Clotting Factor C is a multi-domain serine protease that triggers horseshoe crab hemolymph clotting in the presence of trace amounts of bacterial lipopolysaccharides. Here we describe and functionally characterize an homologous molecule, designated as IrFC, from the hard tick Ixodes ricinus. Tick Factor C consists of an N-terminal cysteine-rich domain, four complement control protein (sushi) modules, an LCCL domain, a truncated C-lectin domain and a C-terminal trypsin-type domain. Developmental expression profiling by quantitative real-time PCR revealed that the irfc mRNA is expressed in all stages including eggs. In tissues dissected from adult I. ricinus females, the irfc mRNA is present mainly in tick hemocytes and accordingly, indirect immunofluorescence microscopy localized IrFC intracellularly, in tick hemocytes. Irfc mRNA levels were markedly increased upon injection of sterile saline, or different microbes, demonstrating that the irfc gene transcription occurs in response to injury. This indicates a possible role of IrFC in hemolymph clotting and/or wound healing, although these defense mechanisms have not been yet definitely demonstrated in ticks. RNAi silencing of irfc expression resulted in a significant reduction in phagocytic activity of tick hemocytes against the Gram-negative bacteria Chryseobacterium indologenes and Escherichia coli, but not against the yeast, Candida albicans. This result suggests that IrFC plays a role in the tick primordial complement system and as such possibly mediates transmission of tick-borne pathogens.
- MeSH
- Borrelia imunologie MeSH
- Candida albicans imunologie MeSH
- Escherichia coli imunologie MeSH
- exprese genu MeSH
- fagocytóza MeSH
- klíště enzymologie genetika imunologie mikrobiologie MeSH
- komplement fyziologie MeSH
- messenger RNA biosyntéza genetika MeSH
- Micrococcus luteus imunologie MeSH
- molekulární sekvence - údaje MeSH
- prekurzory enzymů biosyntéza genetika MeSH
- přirozená imunita MeSH
- proteiny členovců biosyntéza genetika MeSH
- serinové endopeptidasy biosyntéza genetika MeSH
- upregulace imunologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Enhancement of the immune response leading to protection against bacterial and fungal infections was shown using different schedules of immunization with microbial pigments and a polysaccharide. The group of mice given carotenoids of Rhodotorula glutinis (preparation I) and polysaccharide of Spitulina platensis (IV) survived for 2 weeks after Pseudomonas aeruginosa infection. The groups of mice given carotenoids (I), polysaccharide (IV), I+IV and with the crude phycocyanin of S. platensis (III)+IV survived for 2 weeks after Candida albicans infection. All other groups recorded a maximum level of mortality reaching 2 mice per group either after immunization or post-infection. Adding the carotenoids, phycocyanin and polysaccharides to food as additives might therefore enhance the human immune response against microbial infections.
- MeSH
- analýza přežití MeSH
- Candida albicans imunologie MeSH
- časové faktory MeSH
- imunologické faktory aplikace a dávkování izolace a purifikace MeSH
- kandidóza imunologie prevence a kontrola MeSH
- karotenoidy farmakologie izolace a purifikace MeSH
- myši MeSH
- pseudomonádové infekce imunologie prevence a kontrola MeSH
- Pseudomonas aeruginosa imunologie MeSH
- Rhodotorula chemie MeSH
- Spirulina chemie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
Nedávno objevené Th17 lymfocyty se diferencují z naivních T-lymfocytů pod vlivem IL-1, IL-6 a IL-23, které produkují aktivované antigen prezentující buňky. Výzkum Th17 lymfocytů se brzo po jejich objevu zaměřil na objasně ní jejich významu pro protektivní imunitu a na jejich roli v rozvoji imunopatologických stavů . Brzy bylo v ně kolika studiích popsáno zvýšené množství Th17 lymfocytůu různých autoimunitních onemocnění a bylo prokázáno, že Th17 lymfocyty jsou vysoce prozánětlivé a účinně podporují vznik zánětů v tkáních. Po identifikaci významu Th17 lymfocytů pro rozvoj autoimunitních onemocnění se výzkum zaměřil na studium role Th17 imunitní odpově di v protektivní imunitě . Cílem je identifikace patogenů , pro jejichž eliminaci je správná funkce Th17 imunitní odpovědi nezbytná. V tomto review shrnujeme současné informace o Th17 lymfocytech a o fyziologickém významu Th17 buněčné odpovědi na základě studií u pacientů s primárními imunodeficity, u kterých je Th17 imunitní odpověď narušena CARD9 deficitem, hyper IgE syndromem a chronickou granulomatózní nemocí. Porušený vývoj a funkce Th17 větve imunitní odpově di se u lidí projevuje chronickými infekcemi Candida albicans a Staphylococcus aureus.
Recently discovered Th17 lymphocytes differentiate from naive T cells in the presence of IL-1, IL-6 and IL-23 produced by activ ated antigen presenting cells. Soon after their initial discovery, Th17 cells have been implicated in the pathogenesis of autoimmune disease s. Activation of the Th17 axis (overproduction of IL-23, amplification of Th17 cells and excessive production of Th17 effector cytokines) has be en implicated in patients with autoimmune diseases and it has been shown that Th17 cells are highly proinflammatory and that they promote tissue inflammation. Efforts then have been made to characterize the role of Th17 cells in protective immunity in humans. With regard to the role of Th17 cells in protective immunity, the intriguing question has been which pathogens require the appropriate function of Th17 cells for elimin ation. In this review, we summarize current knowledge about the function of Th17 lymphocytes in the context of three primary immunodeficiencie s with disturbed development of Th17 immune response, CARD9 deficiency, hyper IgE syndrome and chronic granulomatous disease. Disturba nces in the development or function of Th17 immune response result in chronic infections with Candida albicans and Staphylococcus aureus .
- Klíčová slova
- hyper IgE, chronická mukokutánní kandidóza,
- MeSH
- autoimunitní nemoci imunologie mikrobiologie MeSH
- buněčná imunita genetika imunologie MeSH
- Candida albicans imunologie MeSH
- chronická granulomatózní nemoc imunologie mikrobiologie MeSH
- financování organizované MeSH
- interleukin-17 metabolismus MeSH
- kandidóza chronická mukokutánní imunologie mikrobiologie MeSH
- lidé MeSH
- Staphylococcus aureus imunologie MeSH
- T-lymfocyty - podskupiny imunologie MeSH
- Check Tag
- lidé MeSH
Kvasinku Candida albicans považujeme za normálnu súčasťľudskej mikroflóry. Napriek tomu kvasinkovú vulvovaginitídu minimálne raz za život prekoná takmer každá žena, na jej rekurentnú formu trpí vo fertilnom veku takmer 50 % žien. Podávame prehľad historických aj súčasných názorov na patogenézu rekurentnej kandidovej vulvovaginitídy s dôrazom na imunologické mechanizmy a význam alergickej komponenty. Pripomíname nevyhnutnosť medziodborovej spolupráce pri riešení žien s týmto ochorením významne zasahujúcim kvalitu života. V rámci komplexu opatrení patrí významné miesto aj imunoterapii. Uvádzame nové odporúčania pre podávanie prípravku Candivac.
Yeast Candida albicans is considered as a normal component of human microflora; however once a life experience an attack of can dida-associated vulvovaginitis almost every woman and from recurrent form suffer up to 50% of woman. We serve an overview of historic and actua l opinions on pathogenesis of recurrent vulvovaginal candidosis with emphasis on immunologic mechanisms and relevance of its allergic comp onent. We remind the importance of multidisciplinary approach by dealing with this disease significantly influencing the quality of life. Among complex of measures immunotherapy ranks an important position. New recommendations with remedy Candivac are presented.
The Candida albicans heat shock protein 90 kDa (hsp90-CA) is an important target for protective antibodies in disseminated candidiasis of experimental mice and humans. Hsp90-CA is present in the cell wall of Candida pseudohyphae or hyphae--typical pathogenic morphotypes in both mucosal and systemic Candida infections. However, the potential protective effects of hsp90-CA-specific antibodies in vaginal candidiasis has not yet been reported. In the present study we used various vaccine formulations (recombinant hsp90-CA protein and hsp90-CA-encoding DNA vaccine) and routes of administration (intradermal, intranasal, and intravenous) to induce both hsp90-CA-specific systemic and vaginal mucosa immune responses in experimental BALB/c mice. The results showed that intradermal recombinant hsp90-CA protein priming, followed by intranasal or intradermal recombinant hsp90-CA protein boosting induced significant increases in both serum and vaginal hsp90-CA-specific IgG and IgA antibodies compared to the control group, as well as enhanced hsp90-CA-specific splenocyte responses in vitro. In the intradermally boosted group, subsequent experimental vaginal Candida infection induced additional increases in the hsp90-CA specific IgG isotype, suggesting that Candida has the ability to induce a local hsp90-specific antibody (IgG) response during vulvovaginal candidiasis. Further work is required to elucidate the importance of immunity to highly conserved antigens during infection of the human female reproductive tract where a balance between immunity to and tolerance for commonly antigens such as hsp90 is necessary for the maintenance of fertility.
- MeSH
- aplikace intranazální MeSH
- Candida albicans imunologie MeSH
- DNA vakcíny aplikace a dávkování imunologie MeSH
- financování organizované MeSH
- fungální proteiny imunologie MeSH
- fungální vakcíny aplikace a dávkování imunologie MeSH
- injekce intradermální MeSH
- injekce intravenózní MeSH
- kandidóza vulvovaginální imunologie MeSH
- lymfocyty imunologie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- proliferace buněk MeSH
- proteiny tepelného šoku HSP90 imunologie MeSH
- protilátky fungální analýza krev MeSH
- sekundární imunizace MeSH
- slezina imunologie MeSH
- syntetické vakcíny aplikace a dávkování imunologie MeSH
- tvorba protilátek MeSH
- vagina imunologie mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
Candida albicans obsahuje ve své cytoplazmě receptory pro pohlavní steroidní hormony. Vztah vulvova-ginální kandidózy a ženských pohlavních hormonů byl předmětem řady studií a je již prokázán. Souvislost mezi kožní kandidózou a ženskými pohlavními hormony, jakož i možný vztah kožní a vulvovaginální kan¬didózy nebyly dosud podrobněji studovány. Práce se zabývá faktory ovlivňujícími vznik a průběh muko¬kutánní kandidózy s ohledem na možný vliv ženských pohlavních hormonů.
Candida albicans contains cytoplasmatic receptors for sexual steroid hormones. The relation between vulvovaginal candidiasis and women's sexual hormones has been an object of many studies and has been already proved. The relationship between cutaneous candidiasis and women's sexual hormones as well as a possible relationship between cutaneous and vulvovaginal candidiasis has not been studied in detail yet. The páper takés an interest in factors influencing the development and the progress of mucocutaneous can¬didiasis and its possible connection with women's sexual hormones.
