| 1. |
- Davidsson, Sabina, 1972-, et al.
(författare)
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Cutibacterium acnes Induces the Expression of Immunosuppressive Genes in Macrophages and is Associated with an Increase of Regulatory T-Cells in Prostate Cancer
- 2021
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Ingår i: Microbiology Spectrum. - : American Society for Microbiology. - 2165-0497. ; 9:3
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Tidskriftsartikel (refereegranskat)abstract
- Tumors and infectious agents both benefit from an immunosuppressive environment. Cutibacterium acnes (C. acnes) is a bacterium in the normal skin microbiota, which has the ability to survive intracellularly in macrophages and is significantly more common in prostate cancer tissue compared with normal prostate tissue. This study investigated if prostate cancer tissue culture positive for C. acnes has a higher infiltration of regulatory T-cells (Tregs) and if macrophages stimulated with C. acnes induced the expression of immunosuppressive genes that could be linked to an increase of Tregs in prostate cancer. Real-time PCR and enzyme-linked immunosorbent spot assay (ELISA) were used to examine the expression of immunosuppressive genes in human macrophages stimulated in vitro with C. acnes, and associations between the presence of C. acnes and infiltration of Tregs were investigated by statistically analyzing data generated in two previous studies. The in vitro results demonstrated that macrophages stimulated with C. acnes significantly increased their expression of PD-L1, CCL17, and CCL18 mRNA and protein (p ,0.05). In the cohort, Tregs in tumor stroma and tumor epithelia were positively associated with the presence of C. acnes (P = 0.0004 and P = 0.046, respectively). Since the macrophages stimulated with C. acnes in vitro increased the expression of immunosuppressive genes, and prostate cancer patients with prostatic C. acnes infection had higher infiltration of Tregs than their noninfected counterparts, we suggest that C. acnes may contribute to an immunosuppressive tumor environment that is vital for prostate cancer progression.
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| 2. |
- Davidsson, Sabina, 1972-, et al.
(författare)
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Infiltration of M2 Macrophages and Regulatory T Cells Plays a Role in Recurrence of Renal Cell Carcinoma
- 2020
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Ingår i: European Urology Open Science. - : Elsevier. - 2666-1691 .- 2666-1683. ; 20, s. 62-71
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Tidskriftsartikel (refereegranskat)abstract
- Regulatory T cells (Tregs) and M2 macrophages have been hypothesized to contribute to tumor progression. We found that M2 macrophages and Tregs are associated with more aggressive renal cell carcinoma, and that they have a synergistic effect on clinical outcome. Background: It has been hypothesized that M2 macrophages and regulatory T cells (Tregs) may contribute to tumor progression by suppression of antitumor immunity. Objective: To investigate the association between infiltration of CD163+ M2 macrophages and CD4+FOXP3+ Tregs with clinical outcomes in renal cell carcinoma patients. Design, setting, and participants: A cohort of 346 patients diagnosed with renal cell carcinoma at Örebro University Hospital between 1986 and 2011 was evaluated for CD163+ M2 macrophage and CD4+FOXP3+ Treg infiltration by immunohistochemistry. Outcome measurements and statistical analysis: Associations between clinicopathological features and infiltration of CD163+ M2 macrophages and/or CD4+FOXP3+ Tregs were estimated with chi-square or Fisher's exact tests. For survival analyses, Kaplan-Meier curves with log-rank tests and multivariate Cox proportional hazards regression models were used. Results and limitations: We found that infiltration of CD163+ M2 macrophages and CD4+FOXP3+ Tregs were associated with adverse clinical outcomes. Our data further demonstrate that CD163+ M2 macrophages and CD4+FOXP3+ Tregs colocalize in tumor and normal tissue, and that this colocalization may have synergistic effects on tumor aggressiveness. The use of tissue microarrays rather than whole sections may be viewed as a limitation. Conclusions: Infiltration of CD163+ M2 macrophages and CD4+FOXP3+ Tregs is associated with recurrence of renal cell carcinoma, and colocalization of these cell types may have an association with clinical outcome. Patient summary: The aim of this study was to investigate the association between infiltration of M2 macrophages and regulatory T cells with clinical outcomes in renal cell carcinoma. We demonstrated that renal cell carcinoma patients with high infiltration of both these cell types are at an increased risk of poor clinical outcomes.
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| 3. |
- Erlandsson, Ann, 1968-, et al.
(författare)
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Infiltrating immune cells in prostate cancer tissue after androgen deprivation and radiotherapy
- 2023
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Ingår i: International journal of immunopathology and pharmacology. - : Sage Publications. - 0394-6320 .- 2058-7384. ; 37
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Androgen deprivation therapy (ADT) has long been a cornerstone in treatment of advanced prostate cancer (PCa), and is known to improve the results of radiotherapy (RT) for high-risk disease. The purpose of our study was to use a multiplexed immunohistochemical (mIHC) approach to investigate the infiltration of immune cells in PCa tissue after eight weeks of ADT and/or RT with 10 Gy.Methods: From a cohort of 48 patients divided into two treatment arms, we obtained biopsies before and after treatment and used a mIHC method with multispectral imaging to analyze the infiltration of immune cells in tumor stroma and tumor epithelium, focusing on areas with high infiltration.Results: Tumor stroma showed a significantly higher infiltration of immune cells compared to tumor epithelium. The most prominent immune cells were CD20(+) B-lymphocytes, followed by CD68(+) macrophages, CD8(+) cytotoxic T-cells, FOXP3(+) regulatory T-cells (Tregs), and T-bet(+) Th1-cells. Neoadjuvant ADT followed by RT significantly increased the infiltration of all five immune cells. Numbers of Th1-cells and Tregs significantly increased after single treatment with ADT or RT. In addition, ADT alone increased the number of cytotoxic T-cells and RT increased the number of B-cells.Conclusions: Neoadjuvant ADT in combination with RT results in a higher inflammatory response compared to RT or ADT alone. The mIHC method may be a useful tool for investigating infiltrating immune cells in PCa biopsies to understand how immunotherapeutic approaches can be combined with current PCa therapies.
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| 4. |
- Erlandsson, Ann, 1968-, et al.
(författare)
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Using qPCR to Identify Potential Effects of Thermal Conditions during Embryogenesis on Mitochondrial DNA Copy Number in Juvenile Brown Trout Salmo trutta
- 2024
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Ingår i: Fishes. - : MDPI. - 2410-3888. ; 9:4
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Tidskriftsartikel (refereegranskat)abstract
- Changes in the number, structure, and function of mitochondria during the early life stages of animals can play an important role for an organism's metabolic rate, growth, and health. Previous studies have shown that juvenile brown trout (Salmo trutta) subjected to elevated temperatures during the embryonic stage respond phenotypically with a reduced metabolic rate. The aim of this study was to explore if embryonic temperature affects the mitochondria content of young brown trout and as such explains the previously found differences in metabolic rates. Here, we optimize a quantitative PCR (qPCR) method for the mitochondria cytochrome c oxidase subunit I gene, and then use the method as a proxy for mitochondrial DNA content. We hypothesize that young trout subjected to elevated temperatures during the embryonic stage respond phenotypically with a reduced mitochondrial DNA content. To test this hypothesis, we subjected brown trout to either control ambient (4.4 +/- 1.5 degrees C) or elevated temperatures (7.1 +/- 0.6 degrees C) during embryogenesis. Subsequently, we extracted DNA from liver and white muscle tissue of juvenile brown trout from the two different incubation temperature treatments and successively optimized qPCR for mitochondrial DNA. We found that the amount of mitochondria DNA in liver tissue was 18 times higher than in white muscle tissue, but there was no significant difference in mitochondria content in liver or muscle tissue between brown trout exposed to elevated and ambient control temperatures during embryogenesis. We conclude that reduced metabolic rate is not likely associated with mitochondria DNA content. We also suggest that qPCR is a simple and cost-effective method to quantify mitochondria DNA in frozen and partly degraded tissue from different treatment groups and a useful proxy for identification of differences in mitochondria number.
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| 5. |
- Filipsson, Karl, et al.
(författare)
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Do predator odours and warmer winters affect growth of salmonid embryos?
- 2023
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Ingår i: Ecology of Freshwater Fish. - : John Wiley & Sons. - 0906-6691 .- 1600-0633. ; :1
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Tidskriftsartikel (refereegranskat)abstract
- Conditions early in ontogeny can have considerable effects later on in life. Many salmonids spawn during the autumn, and temperature during subsequent embryogenesis may have far-reaching effects on life-history traits, especially when considering ongoing climate change. Even biotic conditions during embryogenesis, such as predation threat, may affect later life stages. Here, we examined how predator odours and increased temperatures affect embryonic growth and development of a fish (brown trout Salmo trutta). We found that embryos had lower body mass and greater yolk volume close to hatching when subjected to predator odours. Trout embryos incubated at temperatures representing natural winter conditions were larger than embryos incubated at higher temperatures, although the latter hatched earlier. Fry sizes at emergence did not differ between treatments, perhaps because of compensatory growth during spring. This study shows that predator presence can have similar effects on embryonic growth of salmonids as warming winters, with possible impact later in ontogeny.
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| 6. |
- Filipsson, Karl
(författare)
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Early life stages of brown trout - Anti-predator responses under warming winters
- 2022
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- During winter, juvenile salmonids in boreal streams are vulnerable to predation, mainly from mammals and birds. Encounters with terrestrial predators can be reduced or avoided if fish limit activity to the darker periods of the day or to periods with surface ice. As piscivorous fish also are active in winter, they may be a threat under low light conditions when juvenile salmonids do not avoid terrestrial predators. Abiotic conditions, especially temperature, have major effects on fish in winter. High temperatures alter ice conditions in winter and lead to increased metabolism and physiological performance of fish. Water temperature also influences embryogenesis, with repercussions for fish throughout their life. Considering the rapid warming of winters in boreal regions, insights into how salmonids are adapted to winter conditions can aid in efforts to predict and mitigate anthropogenic effects that alter the winter environment.In this doctoral thesis, I explore anti-predator responses of brown trout (Salmo trutta) during its early life stages. I have examined the effects of predators, temperature, light and ice on the behaviour and physiology of juvenile trout during winter. In addition, I have studied how temperature and predators affect embryogenesis and the behaviour of fry after hatching. Anti-predator responses were evident in both the behaviour and physiology of juveniles and during embryogenesis. Trout exhibited diel behavioural changes when piscivorous fish were present, and were more vigilant towards piscivorous fish in darkness. Furthermore, temperature affected trout behaviour and physiology, with higher activity levels and lower mRNA expression of stress-related genes at higher temperatures. Trout also behaved differently depending on the temperature they experienced as eggs, as increased egg-incubation temperatures resulted in trout being more active and prone to risk taking.
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| 7. |
- Filipsson, Karl, 1991-
(författare)
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From behaviour to genes: anti-predator responses of brown trout (Salmo trutta) under winter conditions
- 2020
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Licentiatavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Temperature has major effects on the performance of poikilotherms. In encounters with predators, low winter temperatures constrain predator detection and escape capabilities in prey fishes. Most studies of the anti-predator responses of fish under winter conditions focus on endothermic terrestrial predators, whereas effects of piscivorous fish are generally overlooked. The studies presented in this thesis explore behavioural and physiological responses of juvenile brown trout (Salmo trutta) at winter temperatures of 3 and 8 °C in the presence and absence of a winter-active piscivorous fish (burbot, Lota lota). In Paper I, I report behavioural responses of trout in relation to the time of day. At the lower temperature and in the presence of burbot, trout reduced their activity. Trout used overhead shelter the most during the day and in the presence of burbot. Trout also spatially avoided burbot at night and at dawn but not during the day. In Paper II, I examined plasma cortisol and mRNA expression of stress-related genes. A redundancy analysis showed that both temperature and the presence of burbot explained a significant amount of the observed variation. Trout had higher cortisol levels when exposed to the burbot. Analyses of individual gene expressions revealed that trout had higher mRNA expression at 3 than at 8 °C for 11 of the 16 examined genes. Only one gene, RBP1, was expressed to a higher degree in the presence of burbot, but there were also interaction effects between temperature and burbot presence for two genes coding for serotonin and glucocorticoid receptors. My studies show that piscivorous fish shape anti-predator responses of juvenile brown trout, both behaviourally and at the gene level, under winter conditions. The observed thermal effects on mRNA levels underscore the importance of temperature in fish stress responses, with implications for stream salmonids in a warmer climate.
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| 8. |
- Filipsson, Karl, et al.
(författare)
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Temperature and predator-mediated regulation of plasma cortisol and brain gene expression in juvenile brown trout (Salmo trutta)
- 2020
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Ingår i: Frontiers in Zoology. - : BioMed Central. - 1742-9994. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Temperature affects many aspects of performance in poikilotherms, including how prey respond when encountering predators. Studies of anti-predator responses in fish mainly have focused on behaviour, whereas physiological responses regulated through the hypothalamic-pituitary-interrenal axis have received little attention. We examined plasma cortisol and mRNA levels of stress-related genes in juvenile brown trout (Salmo trutta) at 3 and 8 degrees C in the presence and absence of a piscivorous fish (burbot,Lota lota). Results A redundancy analysis revealed that both water temperature and the presence of the predator explained a significant amount of the observed variation in cortisol and mRNA levels (11.4 and 2.8%, respectively). Trout had higher cortisol levels in the presence than in the absence of the predator. Analyses of individual gene expressions revealed that trout had significantly higher mRNA levels for 11 of the 16 examined genes at 3 than at 8 degrees C, and for one gene (retinol-binding protein 1), mRNA levels were higher in the presence than in the absence of the predator. Moreover, we found interaction effects between temperature and predator presence for two genes that code for serotonin and glucocorticoid receptors. Conclusions Our results suggest that piscivorous fish elicit primary stress responses in juvenile salmonids and that some of these responses may be temperature dependent. In addition, this study emphasizes the strong temperature dependence of primary stress responses in poikilotherms, with possible implications for a warming climate.
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| 9. |
- Filipsson, Karl, et al.
(författare)
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Temperature during embryonic development in brown trout influences juvenile behaviour in encounters with predators
- 2024
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Ingår i: Journal of Zoology. - : John Wiley & Sons. - 0952-8369 .- 1469-7998. ; 322:3, s. 241-250
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Tidskriftsartikel (refereegranskat)abstract
- Variation in thermal conditions during embryogenesis can have far-reaching impact throughout ontogeny and may give rise to behavioural variation. Many animals, such as salmonids, exhibit behavioural trade-offs related to foraging and predator avoidance. How embryonic temperature affects these behaviours has remained unexplored. Not only abiotic conditions during embryogenesis but also biotic factors such as predator conditioning may affect fish behaviour, especially anti-predator responses. We examined how elevated temperatures and predator odours throughout embryogenesis affect the behaviour of 28-37 mm young-of-the-year brown trout (Salmo trutta) in encounters with predators, namely Atlantic salmon (Salmo salar; 20 cm) and burbot (Lota lota; 40 cm). Juvenile brown trout were more active and aggressive if they were incubated in warmer water as eggs than if they were incubated in colder water, and trout remained inactive longer when encountering predators if they were cold incubated. Brown trout were less active and aggressive when an Atlantic salmon was present than when a burbot or no predator was present. Behavioural responses did not differ between trout that had been subjected to water with versus without predator odours during embryogenesis, possibly because brown trout were not subjected to conspecific alarm cues during egg incubation. This study shows that thermal conditions during embryogenesis can influence fish behaviour early in life and thus contribute to behavioural variation, with potential effects on life history. Considering the rapid warming of northern regions, elevated embryonic temperatures may contribute substantially to variation in salmonid behaviour in the near future. Variation in environmental conditions during embryogenesis of salmonids can have far-reaching impact throughout ontogeny and may give rise to variation in anti-predator behaviour. In a laboratory experiment, we showed that elevated temperatures throughout embryogenesis increased the activity and aggression of 28-37 mm brown trout fry and reduced the time to first movement in encounters with predators (burbot and Atlantic salmon). Predator odour during embryogenesis did not affect brown trout fry behaviour.image
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| 10. |
- Greenberg, Larry, 1955-, et al.
(författare)
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Body shape and fin size in juvenile Atlantic salmon (Salmo salar) : effects of temperature during embryogenesis
- 2021
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Ingår i: Canadian Journal of Zoology. - : CANADIAN SCIENCE PUBLISHING. - 0008-4301 .- 1480-3283. ; 99:5, s. 381-389
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Tidskriftsartikel (refereegranskat)abstract
- Temperature during egg incubation and early development influences later life stages of fishes, potentially influencing survival. Throughout its distribution, Atlantic salmon (Salmo salar Linnaeus, 1758) have experienced population declines, and in view of ongoing global warming, we tested if temperature during the earliest developmental stages modified body shape and fin size when temperatures averaged 2.6 vs. 5.6 degrees C. This temperature difference simulates increases predicted in climate change scenarios. Based on previous studies, we hypothesized that salmon originating from eggs subjected to cold incubation temperatures would have slimmer bodies and larger pectoral and dorsal fins than salmon from eggs that experienced warmer temperatures. After hatching, the juveniles were raised for 1 year under identical temperatures, after which we measured their body shape and fin areas. We found no support for our hypothesis regarding body shape. Indeed, we found the opposite, with cold-incubated salmon having deeper bodies than warm-incubated salmon. For fin size, the pectoral fins of cold-incubated salmon were larger than for warm-incubated salmon as predicted, but there was no difference in dorsal fin size. These results suggest that global warming may lead to altered body shape and fin size, possibly affecting swimming performance, and thus raise questions about the ecological consequences of the changes.
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