Succession of Microbial Decomposers Is Determined by Litter Type, but Site Conditions Drive Decomposition Rates.

Soil microorganisms are diverse, although they share functions during the decomposition of organic matter. Thus, preferences for soil conditions and litter quality were explored to understand their niche partitioning. A 1-year-long litterbag transplant experiment evaluated how soil physicochemical traits of contrasting sites combined with chemically distinct litters of sedge (S), milkvetch (M) from a grassland, and beech (B) from forest site decomposition. Litter was assessed by mass loss; C, N, and P contents; and low-molecular-weight compounds. Decomposition was described by the succession of fungi, Actinobacteria, Alphaproteobacteria, and Firmicutes; bacterial diversity; and extracellular enzyme activities. The M litter decomposed faster at the nutrient-poor forest site, where the extracellular enzymes were more active, but microbial decomposers were not more abundant. Actinobacteria abundance was affected by site, while Firmicutes and fungi by litter type and Alphaproteobacteria by both factors. Actinobacteria were characterized as late-stage substrate generalists, while fungi were recognized as substrate specialists and site generalists, particularly in the grassland. Overall, soil conditions determined the decomposition rates in the grassland and forest, but successional patterns of the main decomposers (fungi and Actinobacteria) were determined by litter type. These results suggest that shifts in vegetation mostly affect microbial decomposer community composition.IMPORTANCE Anthropogenic disturbance may cause shifts in vegetation and alter the litter input. We studied the decomposition of different litter types under soil conditions of a nutrient-rich grassland and nutrient-poor forest to identify factors responsible for changes in the community structure and succession of microbial decomposers. This will help to predict the consequences of induced changes on the abundance and activity of microbial decomposers and recognize if the decomposition process and resulting quality and quantity of soil organic matter will be affected at various sites.

Effects of dietary fat source on lutein, zeaxanthin and total carotenoids content of the egg yolk in laying hens during the early laying period.

1. The study was conducted to investigate the effects of different dietary levels of an unsaturated or saturated fat source and the effects of different dietary energy levels in laying hen diets on the carotenoid content of the egg yolk. 2. Seventy-two ISA Brown laying hens aged 22 weeks old were allocated, for a 10 week period, to three treatments: control diet (HE group) with a 3.4% supplemented fat containing 2.1% soybean and 1.3% palm oil as fat sources and a ratio of unsaturated to saturated fatty acid (u/s) of 3.33; a lowered energy diet with 2.4% supplemented fat containing 1.4% soybean and 1.0% palm oil and u/s of 3.41 (LE+high u/s); a lowered energy diet with 2.4% supplemented fat containing 0.5% soybean and 1.9% palm oil and a u/s of 2.39 (LE+low u/s). A marigold plant extract supplement was used as a source of lutein. 3. Performance parameters (feed consumption, feed conversion, body weight), egg production rate and egg quality parameters were similar between treatments. Dietary fat digestibility at the middle of the study period was not different. Egg yolk total fat content was similar in all treatments at the middle and at the end of the study period. 4. Lutein, zeaxanthin, cis-lutein and total carotenoids content were significantly lower in eggs produced from the LE+low u/s group compared to those from the HE and the LE+high u/s groups (P < 0.01 for all parameters). 5. It was concluded that feeding laying hens with a diet containing 1% less supplemented fat and a lower u/s ratio compared to a control diet and to a diet with 1% less supplemented fat with a higher u/s ratio resulted in a significant reduction of carotenoid expression in the egg yolk at the end of experimental period. Performance and egg quality parameters were not affected by treatments.

[Pilot Study on MicroRNAs as Biomarkers of Response to Sunitinib Treatment in Patients with Metastatic Renall Cell Carcinoma]. / MikroRNA jako biomarkery odpovedi na lécbu sunitinibem u pacientu s metastatickým karcinomem ledvin - pilotní studie.

BACKGROUND: Renal cell carcinoma (RCC) accounts for 2-3% of all malignant tumours. Metastatic RCC (mRCC) is commonly treated with tyrosine kinase inhibitors (TKI). Effective TKIs administration can be achieved only by accurate prediction of therapeutical response. Therefore, the aim of this study was to analyse papers concerning predictive potential of microRNA (miRNA). MATERIAL AND METHODS: We chose seven candidate miRNAs and analysed their expression on 44 patients divided into cohort with poor and good response to sunitinib treatment. Patients were divided into two groups according to progression-free survival. RNA from tissue samples was isolated and expression of selected miRNAs was measured using quantitative PCR with miRNA-specific TaqMan probes. RESULTS: We successfully validated two miRNAs to be differentially expressed in responding and non-responding patients to sunitinib treatment. Other analysed miRNAs have not shown predictive potential. CONCLUSION: From miRNAs studied so far, two miRNAs had predictive value according to present study.Key words: microRNA - renal cell carcinoma - sunitib The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers. Supported by Ministry of Health of the Czech Republic, grant No. 15-34678A. All rights reserved.Submitted: 19. 3. 2018Accepted: 20. 3. 2018.

Induction of lipogenesis in white fat during cold exposure in mice: link to lean phenotype.

This corrects the article DOI: 10.1038/ijo.2016.228.

Induction of lipogenesis in white fat during cold exposure in mice: link to lean phenotype.

BACKGROUND/OBJECTIVE: Futile substrate cycling based on lipolytic release of fatty acids (FA) from intracellular triacylglycerols (TAG) and their re-esterification (TAG/FA cycling), as well as de novo FA synthesis (de novo lipogenesis (DNL)), represent the core energy-consuming biochemical activities of white adipose tissue (WAT). We aimed to characterize their roles in cold-induced thermogenesis and energy homeostasis. METHODS: Male obesity-resistant A/J and obesity-prone C57BL/6J mice maintained at 30 °C were exposed to 6 °C for 2 or 7 days. In epididymal WAT (eWAT), TAG synthesis and DNL were determined using in vivo 2H incorporation from 2H2O into tissue TAG and nuclear magnetic resonance spectroscopy. Quantitative real-time-PCR and/or immunohistochemistry and western blotting were used to determine the expression of selected genes and proteins in WAT and liver. RESULTS: The mass of WAT depots declined during cold exposure (CE). Plasma levels of TAG and non-esterified FA were decreased by day 2 but tended to normalize by day 7 of CE. TAG synthesis (reflecting TAG/FA cycle activity) gradually increased during CE. DNL decreased by day 2 of CE but increased several fold over the control values by day 7. Expression of genes involved in lipolysis, glyceroneogenesis, FA re-esterification, FA oxidation and mitochondrial biogenesis in eWAT was induced during CE. All these changes were more pronounced in obesity-resistant A/J than in B6 mice and occurred in the absence of uncoupling protein 1 in eWAT. Expression of markers of glyceroneogenesis in eWAT correlated negatively with hepatic FA synthesis by day 7 in both strains. Leptin and fibroblast growth factor 21 plasma levels were differentially affected by CE in the two mouse strains. CONCLUSIONS: Our results indicate integrated involvement of (i) TAG/FA cycling and DNL in WAT, and (ii) hepatic very-low-density lipoprotein-TAG synthesis in the control of blood lipid levels and provision of FA fuels for thermogenesis in cold. They suggest that lipogenesis in WAT contributes to a lean phenotype.

[Non-specific immunotherapy inhibits angiogenesis - results of the monitoring of serum levels of vascular endothelial growth factor and matrix metalloproteinase 8 in patients with malignant melanoma receiving adjuvant high-dose interferon therapy]. / Nespecifická imunoterapie inhibuje angiogenezi - výsledky monitorování sérových hladin vaskulárního endotelového rustového faktoru a matrixmetaloproteinázy 8 v prubehu adjuvantní lécby vysokodávkovaným interferonem u pacientu s maligním melanomem.

OBJECTIVE: Interestingly, evidence is currently emerging that the activation of angiogenesis leads to immunomodulatory/immunosuppressive effects both at the local and systemic levels. These are very complex and interconnected processes. In this study, our aim was to establish interferon alpha-2b as an anti-angiogenic agent and show the complexity of angiogenesis and immunomodulation through the serum levels of vascular endothelial growth factor (VEGF) and matrix metalloproteinase 8 (MMP-8) in high-risk resected malignant melanoma before and after adjuvant therapy with high-dose interferon alpha-2b (HDI). Clinical outcomes of patients were also evaluated. MATERIAL AND METHODS: We prospectively measured the serum levels of VEGF and MMP-8 by ELISA in 29 patients with high-risk resected malignant melanoma receiving adjuvant HDI. Blood samples were collected before and within one week after the treatment. RESULTS: To see the results clearly, we divided our patients into two groups. The first group of patients whose VEGF serum level decreased after HDI (66%) showed long-term complete remission. The mean VEGF serum level in these patients decreased from 779.4 pg/ml to 446.2 pg/ml. This downward trend in VEGF was statistically significant. The second group of patients who did not show a decrease in VEGF serum level after HDI (34%) had no clinical benefit from the treatment. The mean VEGF serum levels in group 2 patients were 408 pg/ml before the treatment and 500 pg/ml after HDI. Results for MMP-8 were ambivalent. CONCLUSIONS: Non-specific immunotherapy with interferons reduces angiogenesis. Our results are in line with the current view of the interconnection and complexity of angiogenesis and immunomodulation/immunosuppression. Non-specific immunotherapy with interferons disrupts the immunosup-pressive effect of the angiogenesis on the development of immune response against tumours and supports anti-tumour response in both direct and indirect way. The interference of HDI with the activation of angiogenesis and tumour progression could explain good clinical outcomes of patients with a decrease in serum VEGF. The outcomes of MMP-8 are inconclusive, its role remain unclear, and MMP-8 does not seem to function as a tumour suppressor.

[The Role of BRAF/MEK Inhibition in Metastatic Malignant Melanoma - a Case Study]. / Role BRAF/ MEK inhibice u metastazujícího maligního melanomu -  kazuistika.

BACKGROUND: Metastatic malignant melanoma belongs to a group of cancers with high mortality. In recent years, advances in our knowledge of the pathogenesis of melanoma and the discovery of new drugs has resulted in significant progress in the treatment of metastatic malignant melanoma patients. The development of resistance to these drugs, however, remains a challenge. One way how to avoid resistance, or at least delay it, is to administer combination therapy. OBSERVATION AND CONCLUSION: This case study demonstrates that combination therapy with a BRAF and a MEK inhibitor can be used to successfully treat metastatic malignant melanoma patients and suggests they should be employed in therapeutic algorithms for patients with metastatic malignant melanoma and BRAF gene mutations.

Tick saliva increases production of three chemokines including monocyte chemoattractant protein-1, a histamine-releasing cytokine.

The effect of Ixodes ricinus tick saliva on the production of various cytokines and chemokines by mouse splenocytes was tested by a cytokine array. We demonstrated a strong upregulation of three chemokines, monocyte chemoattractant protein-1 (MCP-1), thymus-derived chemotactic agent 3 (TCA-3) and macrophage inflammatory protein 2 (MIP-2). MCP-1 could be induced by tick saliva itself. While TCA-3 and MIP-2 are engaged in Th2 polarization of the host immune response associated with tick feeding, MCP-1 may act as a histamine release factor, increasing blood flow into the feeding lesion thus facilitating tick engorgement in the late, rapid feeding phase.

Tick salivary cystatin sialostatin L2 suppresses IFN responses in mouse dendritic cells.

Type I interferon (IFN), mainly produced by dendritic cells (DCs), is critical in the host defence against tick-transmitted pathogens. Here, we report that salivary cysteine protease inhibitor from the hard tick Ixodes scapularis, sialostatin L2, affects IFN-ß mediated immune reactions in mouse dendritic cells. Following IFN receptor ligation, the Janus activated kinases/signal transducer and activator of transcription (JAK/STAT) pathway is activated. We show that sialostatin L2 attenuates phosphorylation of STATs in spleen dendritic cells upon addition of recombinant IFN-ß. LPS-stimulated dendritic cells release IFN-ß which in turn leads to the induction of IFN-stimulated genes (ISG) through JAK/STAT pathway activation. The induction of two ISG, interferon regulatory factor 7 (IRF-7) and IP-10, was suppressed by sialostatin L2 in LPS-stimulated dendritic cells. Finally, the interference of sialostatin L2 with IFN action led to the enhanced replication of tick-borne encephalitis virus in DC. In summary, we present here that tick salivary cystatin negatively affects IFN-ß responses which may consequently increase the pathogen load after transmission via tick saliva.

Carpoglyphus lactis (Acari: Astigmata) from various dried fruits differed in associated micro-organisms.

AIMS: Carpoglyphus lactis is a stored product mite infesting saccharide-rich stored commodities including dried fruits, wine, beer, milk products, jams and honey. The association with micro-organisms can improve the survival of mites on dried fruits. METHODS AND RESULTS: The microbial communities associated with C. lactis were studied in specimens originating from the packages of dried apricot, plums and figs and compared to the laboratory strain reared on house dust mite diet (HDMd). Clone libraries of bacterial 16S rRNA gene and fungal internal transcribed spacer (ITS) region were constructed and analysed by operational taxonomic unit (OTU) approach. The 16S rRNA gene libraries differed among the compared diets. The sequences classified to the genera Leuconostoc, Elizabethkingia, Ewingella, Erwinia, Bacillus and Serratia were prevailing in mites sampled from the dried fruits. The ITS library showed smaller differences between the laboratory strain on HDMd and the isolates from dried fruits packages, with the exception of the mite strain from dried plums. The population growth was used as an indirect indicator of fitness and decreased in the order from yeast diet to HDMd and dried fruits. CONCLUSIONS: The treatment and pretreatment of mites by antibiotics did not reveal the presence of antagonistic bacteria which might slow down the C. lactis population growth. The shifts of the microbial community in the gut of C. lactis were induced by the diet changes. The identified yeasts and bacteria are suggested as the main food source of stored product mites on dried fruits. SIGNIFICANCE AND IMPACT OF THE STUDY: The study describes the adaptation of C. lactis to feeding on dried fruits including the interaction with micro-organisms. We also identified potentially pathogenic bacteria carried by the mites to dried fruits for human consumption.

Bacteria detected in the honeybee parasitic mite Varroa destructor collected from beehive winter debris.

AIMS: The winter beehive debris containing bodies of honeybee parasitic mite Varroa destructor is used for veterinary diagnostics. The Varroa sucking honeybee haemolymph serves as a reservoir of pathogens including bacteria. Worker bees can pick up pathogens from the debris during cleaning activities and spread the infection to healthy bees within the colony. The aim of this study was to detect entomopathogenic bacteria in the Varroa collected from the winter beehive debris. METHODS AND RESULTS: Culture-independent approach was used to analyse the mite-associated bacterial community. Total DNA was extracted from the samples of 10 Varroa female individuals sampled from 27 different sites in Czechia. The 16S rRNA gene was amplified using universal bacterial primers, cloned and sequenced, resulting in a set of 596 sequences representing 29 operational taxonomic units (OTU97). To confirm the presence of bacteria in Varroa, histological sections of the mites were observed. Undetermined bacteria were observed in the mite gut and fat tissue. CONCLUSION: Morganella sp. was the most frequently detected taxon, followed by Enterococcus sp., Pseudomonas sp., Rahnella sp., Erwinia sp., and Arsenophonus sp. The honeybee putative pathogen Spiroplasma sp. was detected at one site and Bartonella-like bacteria were found at four sites. PCR-based analysis using genus-specific primers enabled detection of the following taxa: Enterococcus, Bartonella-like bacteria, Arsenophonus and Spiroplasma. SIGNIFICANCE AND IMPACT OF THE STUDY: We found potentially pathogenic (Spiroplasma) and parasitic bacteria (Arsenophonus) in mites from winter beehive debris. The mites can be reservoirs of the pathogenic bacteria in the apicultures.

[Possible Pitfalls of Ipilimumab Therapy in Malignant Melanoma -  a Case Report]. / Mozná úskalí lécby ipilimumabem u maligního melanomu -  kazuistika.

BACKGROUND: Metastatic melanoma is a malignancy with one of the highest mortality rates. However, with the introduction of new drugs during the last decade, the prognosis of patients began to improve. Ipilimumab is one of the first so  called modern drugs in melanoma treatment. The therapy is often complicated by adverse effects which are referred as immunerelated adverse events due to its mechanism of action. CASE: We present a case of 68-year- old women with metastatic melanoma who underwent treatment with ipilimumab. The patient encountered several adverse events during the treatment. Some of them are quite common (e.g. skin affections), others (e.g. endocrinopathies) are less frequent. CONCLUSION: This case study highlights the need for close observation not only during the actual treatment with ipilimumab, but also several weeks or months after the last dose. This case study also demonstrates further need of education of doctors who do not usually come in to contact with such patients.

Adipose tissue-related proteins locally associated with resolution of inflammation in obese mice.

OBJECTIVE: Resolution of low-grade inflammation of white adipose tissue (WAT) is one of the keys for amelioration of obesity-associated metabolic dysfunctions. We focused on the identification of adipokines, which could be involved at the early stages of resolution of WAT inflammation. METHODS AND PROCEDURE: Male C57BL/6J mice with obesity induced in response to a 22-week feeding corn oil-based high-fat (cHF) diet were divided into four groups and were fed with, for 2 weeks, control cHF diet or cHF-based diets supplemented with: (i) concentrate of n-3 long-chain polyunsaturated fatty acids, mainly eicosapentaenoic and docosahexaenoic acids (cHF+F); (ii) thiazolidinedione drug rosiglitazone (cHF+TZD); and (iii) both compounds (cHF+F+TZD). RESULTS: The short-term combined intervention exerted additive effect in the amelioration of WAT inflammation in obese mice, namely in the epididymal fat, even in the absence of any changes in either adipocyte volume or fat mass. The combined intervention elicited hypolipidaemic effect and induced adiponectin, whereas the responses to single interventions (cHF+F, cHF+TZD) were less pronounced. In addition, analysis in WAT lysates using protein arrays revealed that the levels of a small set of adipose tissue-related proteins, namely macrophage inflammatory protein 1γ, endoglin, vascular cell adhesion molecule 1 and interleukin 1 receptor antagonist, changed in response to the anti-inflammatory interventions and were strongly reduced in the cHF+F+TZD mice. These results were verified using both the analysis of gene expression and enzyme-linked immunosorbent analysis in WAT lysates. In contrast with adiponectin, which showed changing plasma levels in response to dietary interventions, the levels of the above proteins were affected only in WAT. CONCLUSIONS: We identified several adipose tissue-related proteins, which are locally involved in resolution of low-grade inflammation and remodelling of WAT.

Enhancement of brown fat thermogenesis using chenodeoxycholic acid in mice.

OBJECTIVE: Besides their role in lipid absorption, bile acids (BAs) can act as signalling molecules. Cholic acid was shown to counteract obesity and associated metabolic disorders in high-fat-diet (cHF)-fed mice while enhancing energy expenditure through induction of mitochondrial uncoupling protein 1 (UCP1) and activation of non-shivering thermogenesis in brown adipose tissue (BAT). In this study, the effects of another natural BA, chenodeoxycholic acid (CDCA), on dietary obesity, UCP1 in both interscapular BAT and in white adipose tissue (brite cells in WAT), were characterized in dietary-obese mice. RESEARCH DESIGN: To induce obesity and associated metabolic disorders, male 2-month-old C57BL/6J mice were fed cHF (35% lipid wt wt(-1), mainly corn oil) for 4 months. Mice were then fed either (i) for 8 weeks with cHF or with cHF with two different doses (0.5%, 1%; wt wt(-1)) of CDCA (8-week reversion); or (ii) for 3 weeks with cHF or with cHF with 1% CDCA, or pair-fed (PF) to match calorie intake of the CDCA mice fed ad libitum; mice on standard chow diet were also used (3-week reversion). RESULTS: In the 8-week reversion, the CDCA intervention resulted in a dose-dependent reduction of obesity, dyslipidaemia and glucose intolerance, which could be largely explained by a transient decrease in food intake. The 3-week reversion revealed mild CDCA-dependent and food intake-independent induction of UCP1-mediated thermogenesis in interscapular BAT, negligible increase of UCP1 in subcutaneous WAT and a shift from carbohydrate to lipid oxidation. CONCLUSIONS: CDCA could reverse obesity in cHF-fed mice, mainly in response to the reduction in food intake, an effect probably occuring but neglected in previous studies using cholic acid. Nevertheless, CDCA-dependent and food intake-independent induction of UCP1 in BAT (but not in WAT) could contribute to the reduction in adiposity and to the stabilization of the lean phenotype.

[Adverse effects of modern treatment of malignant melanoma and their treatment/ management]. / Nezádoucí úcinky novodobé lécby maligního melanomu a jejich lécba/ management.

BACKGROUND: Malignant melanoma belongs to the most deadly human tumours and despite all preventive programs its incidence continues to rise. Until 2011, chemotherapy was the only therapeutic option for inoperable or metastatic disease in the Czech Republic. However, new treatment modalities (e. g. targeted therapy) have been introduced recently. AIM: Since most of the modern drugs are still available only in clinical trials, the aim of this article is to provide a brief and comprehensive review of current treatment options for metastatic disease. The attention is focused on their potential side effects, so that doctors who do not usually deal with these drugs would get acquainted with them. This could contribute to a prompt management of associated symptoms or an early referral of the patient to an appropriate clinical centre without undue delay.

Adaptive Induction of Nonshivering Thermogenesis in Muscle Rather Than Brown Fat Could Counteract Obesity.

Warm-blooded animals such as birds and mammals are able to protect stable body temperature due to various thermogenic mechanisms. These processes can be facultative (occurring only under specific conditions, such as acute cold) and adaptive (adjusting their capacity according to long-term needs). They can represent a substantial part of overall energy expenditure and, therefore, affect energy balance. Classical mechanisms of facultative thermogenesis include shivering of skeletal muscles and (in mammals) non-shivering thermogenesis (NST) in brown adipose tissue (BAT), which depends on uncoupling protein 1 (UCP1). Existence of several alternative thermogenic mechanisms has been suggested. However, their relative contribution to overall heat production and the extent to which they are adaptive and facultative still needs to be better defined. Here we focus on comparison of NST in BAT with thermogenesis in skeletal muscles, including shivering and NST. We present indications that muscle NST may be adaptive but not facultative, unlike UCP1-dependent NST. Due to its slow regulation and low energy efficiency, reflecting in part the anatomical location, induction of muscle NST may counteract development of obesity more effectively than UCP1-dependent thermogenesis in BAT.

Sex differences during the course of diet-induced obesity in mice: adipose tissue expandability and glycemic control.

OBJECTIVE: Adverse effects of obesity on glucose homeostasis are linked to low-grade adipose tissue inflammation and accumulation of lipids in non-adipose tissues. The goal of this study was to evaluate the role of adipose tissue plasticity in a less severe deterioration of glucose homeostasis in females compared with males during the course of high-fat (HF) feeding in mice. DESIGN: Mice of the C57BL/6N strain were fed either a chow or obesogenic HF diet for up to 35 weeks after weaning. Metabolic markers and hormones in plasma, glucose homeostasis, adipocyte size and inflammatory status of gonadal (gWAT) and subcutaneous (scWAT) adipose depots and liver steatosis were evaluated at 15 and 35 weeks of HF feeding. RESULTS: HF-fed males were heavier than females until week ∼20, after which the body weights stabilized at a similar level (55-58 g) in both sexes. Greater weight gain and fat accumulation in females were associated with larger adipocytes in gWAT and scWAT at week 35. Although adipose tissue macrophage infiltration was in general less frequent in scWAT, it was reduced in both fat depots of female as compared with male mice; however, the expression of inflammatory markers in gWAT was similar in both sexes at week 35. In females, later onset of the impairment of glucose homeostasis and better insulin sensitivity were associated with higher plasma levels of adiponectin (weeks 0, 15 and 35) and reduced hepatosteatosis (weeks 15 and 35). CONCLUSIONS: Compared with males, female mice demonstrate increased capacity for adipocyte enlargement in response to a long-term HF feeding, which is associated with reduced adipose tissue macrophage infiltration and lower fat deposition in the liver, and with better insulin sensitivity. Our data suggest that adipose tissue expandability linked to adiponectin secretion might have a role in the sex differences observed in obesity-associated metabolic disorders.

Effect of tick saliva on signalling pathways activated by TLR-2 ligand and Borrelia afzelii in dendritic cells.

Dendritic cells are a sentinel in defending against pathogens and tick saliva facilitates transmission of tick-borne pathogens by modulating the host immune response. The maturation of dendritic cells is inhibited by tick saliva. To elucidate the mechanism of this inhibition, we tested the impact of Ixodes ricinus tick saliva on signalling pathways activated by Toll-like receptor (TLR-2) ligand and Borrelia afzelii in spleen dendritic cells. The activation of nuclear factor-κB (NF-κB) p65 and phosphatidylinositol-3 kinase (PI3K)/Akt pathways was decreased by tick saliva upon both TLR-2 and Borrelia stimulation. Among the mitogen-activated protein kinases (MAPK), the activation of extracellular matrix-regulated kinase (Erk1/2) was suppressed by tick saliva, but not p38. In response to spirochaetes, the amount of TNF-α decreased in the presence of tick saliva which was mediated by selective suppression of Erk1/2, NF-κB and Akt as tick saliva mimicked the effect of their specific inhibitors, UO126, IKK-IV and LY294002, respectively. Saliva-induced enhancement of IL-10 was not observed in the presence of specific inhibitor of Protein Kinase A (PKA), H-89, suggesting the involvement of PKA pathway in IL-10 production. Our cumulative data show that tick saliva interferes with several signalling pathways, thus modulating the immune functions of dendritic cells.

Tick saliva suppresses IFN signalling in dendritic cells upon Borrelia afzelii infection.

Type I interferons (IFN-α and IFN-ß) are crucial determinants of the host immune response and tick saliva modulates this response, thus facilitating the transmission of tickborne pathogens. The current study therefore examines the effect of Ixodes ricinus tick saliva on IFN-ß signalling in murine dendritic cells using lipopolysaccharide (LPS) and Borrelia afzelii spirochaetes as inducers. Activated dendritic cells secret IFN that activates Signal Transducer and Activator of Transcription 1 (STAT-1). Our results show that Borrelia-induced activation of STAT-1 was suppressed by tick saliva. As the amount of secreted IFN-ß was not influenced by tick saliva, the results indicated that saliva affected the interferon pathway at the IFN receptor or downstream of it. By using recombinant IFN-ß, we show that tick saliva attenuates IFN-triggered STAT-1 activation. Tick saliva also inhibited LPS-induced IFN-ß production suggesting that saliva interferes with the activation of the pathway that mediates IFN-ß induction. Our data indicate that I. ricinus tick saliva may modulate the host immune response by attenuating the initial signal transduction pathway of type I IFN.

[Changes in immune reactivity in cancer patients]. / Zmeny imunologické reaktivity u onkologických pacientu

It appears that the long-accepted paradigm that cytostatic and radiation therapy cause only immunosuppression, is not so clearly true. With regard to new knowledge in cancer immunology field, it seems that not only cytostatic and radiation therapy plays an important role in the alteration of immune system. There are many other factors influencing immunity like tumour environment itself, the use of immunomodulatory drugs or even the mental condition of cancer patients. The aim of review is to familiarize physicians with possible alterations of the immune system in cancer patients.