Immunomodulatory effects of cyanobacterial toxin cylindrospermopsin on innate immune cells

Moosová, Zdena; Pekarová, Michaela; Šindlerová, Lenka; Vašíček, Ondřej; Kubala, Lukáš; Bláha, Luděk; Adamovský, Ondřej

doi:10.1016/j.chemosphere.2019.03.143

Cited by 30 publications

(18 citation statements)

References 51 publications

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“…Although previous studies show that both SVCV and cyanobacteria deregulate the immune system [6][7][8], we observed that the combination of stressors (B+SVC) has unique characteristics and impact on immunity. Specifically, in comparison to control and effects of individual stressors, solely combined exposure to B+SVC resulted in a dramatic rise in the production of immunoglobulins (Figure 2).…”

Section: Discussioncontrasting

confidence: 74%

“…Although an individual stressor present in the environment may not represent a significant risk for aquatic organisms, a combination of multiple factors can produce unforeseen effects, especially if they target the same biological system or function (e.g., immune system). Despite the immunomodulatory potency of cyanobacterial toxins being confirmed both in vitro and in vivo [ 6 , 7 , 8 , 9 ], data on the cyanobacterial influence on the manifestation of diseases or on the susceptibility of individuals to bacterial and viral agents frequently present in the environment together with cyanobacteria, are sparse. A limited number of studies indicate that cyanobacteria may negatively contribute to the effects of other stressors.…”

Section: Introductionmentioning

confidence: 99%

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Cyanobacteria Microcystis aeruginosa Contributes to the Severity of Fish Diseases: A Study on Spring Viraemia of Carp

Palíková

Kopp

Kohoutek

et al. 2021

Toxins

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Fish are exposed to numerous stressors in the environment including pollution, bacterial and viral agents, and toxic substances. Our study with common carps leveraged an integrated approach (i.e., histology, biochemical and hematological measurements, and analytical chemistry) to understand how cyanobacteria interfere with the impact of a model viral agent, Carp sprivivirus (SVCV), on fish. In addition to the specific effects of a single stressor (SVCV or cyanobacteria), the combination of both stressors worsens markers related to the immune system and liver health. Solely combined exposure resulted in the rise in the production of immunoglobulins, changes in glucose and cholesterol levels, and an elevated marker of impaired liver, alanine aminotransferase (ALT). Analytical determination of the cyanobacterial toxin microcystin-LR (MC-LR) and its structurally similar congener MC-RR and their conjugates showed that SVCV affects neither the levels of MC in the liver nor the detoxification capacity of the liver. MC-LR and MC-RR were depurated from liver mostly in the form of cysteine conjugates (MC-LR-Cys, MC-RR-Cys) in comparison to glutathione conjugates (LR-GSH, RR-GSH). Our study brought new evidence that cyanobacteria worsen the effect of viral agents. Such inclusion of multiple stressor concept helps us to understand how and to what extent the relevant environmental stressors co-influence the health of the fish population.

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Section: Discussioncontrasting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

Cyanobacteria Microcystis aeruginosa Contributes to the Severity of Fish Diseases: A Study on Spring Viraemia of Carp

Palíková

Kopp

Kohoutek

et al. 2021

Toxins

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“…These first-line defense mechanisms are, amongst others, increased expression of pro-inflammatory cytokines (e.g., IL-6 and TNFα), production of reactive oxygen species (ROS), secretion of nitric oxide, and phagocytosis [69,[134][135][136]. Recently, it was elucidated that CYN activates murine macrophages in vitro [137]. In addition, CYN (0.1 µg/L; 0.24 µM) has been shown to significantly decrease lymphocyte proliferation in vitro in both isolated T-cell culture and a whole-blood assay [138].…”

Section: Cylindrospermopsin Effectsmentioning

confidence: 99%

Effects of cyanobacterial toxins on the human gastrointestinal tract and the mucosal innate immune system

et al. 2019

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Background: Cyanobacterial blooms occur with increasing frequency in freshwater ecosystems, posing a hazard to human and environmental health. Exposure of human to cyanobacterial metabolites occurs mostly via accidental ingestion through contaminated drinking water or during recreational activities and, most frequently, results in gastrointestinal symptoms. Despite the clinical manifestation, cyanobacterial metabolites are rather investigated for their toxicity towards specific organs or tissues, especially hepato-, nephro-, and neurotoxicity, than for effects on the gastrointestinal tract and the associated lymphoid tissue. Main body: The aim of this review was to systematically summarize available literature on the effects on the gastrointestinal tract and the mucosal innate immune system and compile the data from both, in vitro and in vivo studies, focusing on human health-relevant models. Our systematic literature review revealed significant data gaps in the understanding on metabolites breaching the gastrointestinal barrier and the role of the immune system in the establishment of clinical symptoms. Microcystins and cylindrospermopsin were linked to gastrointestinal symptoms, immune system effects, or both. Furthermore, cyanobacterial bloom lipopolysaccharides, other less studied metabolites and their mixtures have been also implicated to have a role in gastrointestinal inflammation. Conclusion: The collected data indicate the need for a reassessment of potential enterotoxicity of microcystins and cylindrospermopsin. In addition, the carcinogenic potential of cyanotoxins, especially microcystins, has to be clarified, as an increasing amount of epidemiological studies show correlations between cyanobacterial blooms and gastrointestinal cancer incidence. Furthermore, other, often highly abundant bioactive metabolites such as aeruginosins, have to be toxicologically evaluated at distinct levels also accounting for (sub-)chronic exposure to low concentrations and in combination with naturally co-occurring metabolites, which can be expected in drinking water supplies.

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“…Macrophages stimulated by pro-inflammatory molecules release a variety of endogenous mediators such as nitric oxide (NO), reactive oxygen species (ROS), tumor necrosis factor alpha (TNF-α), and Interleukin-6 (IL-6), among others, that trigger an inflammatory reaction. Activation of the nuclear factor-κB (NF-κB), a dependent intracellular signaling pathway in macrophages, includes the activation of mitogen-activated protein kinases (MAPKs) [37]. When MAPK is the dominant signal activated in TNF, this signal is connected to inflammation, apoptosis or necrosis [38].…”

Section: Introductionmentioning

confidence: 99%

“…In recent decades, research on the potential impact of cyanotoxins on the immune system, especially in the case of MCs, has increased significantly. There are different studies in which cyanotoxins can impact both the function of blood cells of the immune system (such as macrophages, neutrophils, lymphocytes) [53][54][55][56][57][58][59][60][61], and the production of ROS and NO [35,37,55,[62][63][64][65][66]. Moreover, several authors have focused on the study of transcription factors and cytokine production [37,61,62,[66][67][68][69][70].…”

Section: Introductionmentioning

confidence: 99%

Immunotoxic Effects Induced by Microcystins and Cylindrospermopsin: A Review

Díez-Quijada

Benítez-González

Puerto

et al. 2021

Toxins

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Cyanotoxin occurrence is gaining importance due to anthropogenic activities, climate change and eutrophication. Among them, Microcystins (MCs) and Cylindrospermopsin (CYN) are the most frequently studied due to their ubiquity and toxicity. Although MCs are primary classified as hepatotoxins and CYN as a cytotoxin, they have been shown to induce deleterious effects in a wide range of organs. However, their effects on the immune system are as yet scarcely investigated. Thus, to know the impact of cyanotoxins on the immune system, due to its importance in organisms’ homeostasis, is considered of interest. A review of the scientific literature dealing with the immunotoxicity of MCs and CYN has been performed, and both in vitro and in vivo studies have been considered. Results have confirmed the scarcity of reports on the topic, particularly for CYN. Decreased cell viability, apoptosis or altered functions of immune cells, and changed levels and mRNA expression of cytokines are among the most common effects reported. Underlying mechanisms, however, are still not yet fully elucidated. Further research is needed in order to have a full picture of cyanotoxin immunotoxicity.

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Immunomodulatory effects of cyanobacterial toxin cylindrospermopsin on innate immune cells

Cited by 30 publications

References 51 publications

Cyanobacteria Microcystis aeruginosa Contributes to the Severity of Fish Diseases: A Study on Spring Viraemia of Carp

Cyanobacteria Microcystis aeruginosa Contributes to the Severity of Fish Diseases: A Study on Spring Viraemia of Carp

Effects of cyanobacterial toxins on the human gastrointestinal tract and the mucosal innate immune system

Immunotoxic Effects Induced by Microcystins and Cylindrospermopsin: A Review

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