Advances on the early cellular events occurring upon exposure of human macrophages to aluminum oxyhydroxide adjuvant

Masson, J-D; Badran, Ghidaa; Domdom, Marie Angela; Gherardi, Romain K.; Mograbi, Baharia; Authier, Florence; Crépeaux, Guillemette

doi:10.1038/s41598-023-30336-1

Cited by 7 publications

(3 citation statements)

References 62 publications

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“…These effects were attenuated by chlorogenic acid [249]. Al 3+ -induced oxidative stress showed toxic effects that manifested as cell viability collapse, ∆Ψ mito decline, an increase in ROS production, and a decrease in oxygen consumption and mitochondria enzyme activity in experiments with rat nerve cells and human peripheral blood mononuclear cells [252,253].…”

Section: Al(iii) Ga(iii) and In(iiimentioning

confidence: 99%

Mitochondrial Oxidative Stress Is the General Reason for Apoptosis Induced by Different-Valence Heavy Metals in Cells and Mitochondria

Korotkov

2023

IJMS

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This review analyzes the causes and consequences of apoptosis resulting from oxidative stress that occurs in mitochondria and cells exposed to the toxic effects of different-valence heavy metals (Ag+, Tl+, Hg2+, Cd2+, Pb2+, Al3+, Ga3+, In3+, As3+, Sb3+, Cr6+, and U6+). The problems of the relationship between the integration of these toxic metals into molecular mechanisms with the subsequent development of pathophysiological processes and the appearance of diseases caused by the accumulation of these metals in the body are also addressed in this review. Such apoptosis is characterized by a reduction in cell viability, the activation of caspase-3 and caspase-9, the expression of pro-apoptotic genes (Bax and Bcl-2), and the activation of protein kinases (ERK, JNK, p53, and p38) by mitogens. Moreover, the oxidative stress manifests as the mitochondrial permeability transition pore (MPTP) opening, mitochondrial swelling, an increase in the production of reactive oxygen species (ROS) and H2O2, lipid peroxidation, cytochrome c release, a decline in the inner mitochondrial membrane potential (ΔΨmito), a decrease in ATP synthesis, and reduced glutathione and oxygen consumption as well as cytoplasm and matrix calcium overload due to Ca2+ release from the endoplasmic reticulum (ER). The apoptosis and respiratory dysfunction induced by these metals are discussed regarding their interaction with cellular and mitochondrial thiol groups and Fe2+ metabolism disturbance. Similarities and differences in the toxic effects of Tl+ from those of other heavy metals under review are discussed. Similarities may be due to the increase in the cytoplasmic calcium concentration induced by Tl+ and these metals. One difference discussed is the failure to decrease Tl+ toxicity through metallothionein-dependent mechanisms. Another difference could be the decrease in reduced glutathione in the matrix due to the reversible oxidation of Tl+ to Tl3+ near the centers of ROS generation in the respiratory chain. The latter may explain why thallium toxicity to humans turned out to be higher than the toxicity of mercury, lead, cadmium, copper, and zinc.

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Section: Al(iii) Ga(iii) and In(iiimentioning

confidence: 99%

Mitochondrial Oxidative Stress Is the General Reason for Apoptosis Induced by Different-Valence Heavy Metals in Cells and Mitochondria

Korotkov

2023

IJMS

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“…It is found in various bodily secretions and tissues, including blood, tears, and saliva [21]. Adjuvants can activate the nonspeci c immune cells, such as macrophages and dendritic cells, leading to the production of various immune mediators and cytokines [22,23]. In this study, lysozyme activity increased several folds in the AE adjuvanted sh.…”

Section: Discussionmentioning

confidence: 56%

Adjuvanting Property of Aqueous Extract of the Indian Mistletoe, Dendrophthoe falcata

Kanagaraj,

Subramani

et al. 2023

Preprint

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The Indian mistletoe, Dendrophthoe falcata, has been traditionally used in Ayurvedic medicine for its various therapeutic properties. Adjuvants are substances that enhance the immune response to antigens, thereby improving the effectiveness of vaccines or immunotherapies. In this study, the aqueous extract of D. falcata was evaluated for its adjuvanting potential in Nile tilapia, Oreochromis niloticus. An aqueous extract (AE) was prepared from the dried leaves of D. falcata. The adjuvant activity was assessed by co-administering the extract with a heat inactivated Streptococcus agalactiae vaccine in O. niloticus. The immune response was evaluated by measuring the serum lysozyme activity and the serum antibody levels. Results showed that the AE significantly enhanced the specific and nonspecific immune responses to the model antigen. It increased the serum lysozyme activity and elicited a robust production of specific antibodies, suggesting a potentiated nonspecific and specific immune response. The adjuvanting property of the aqueous extract of D. falcata suggests its potential utility in enhancing the effectiveness of vaccines or immunotherapies.

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“…The enriched GO terms and Reactome pathways in the ME1 module were mainly related to mitochondria and energy metabolism. A tendency of aluminum hydroxide to increase basal mitochondrial metabolism, seemingly linked to energetic requests to support phagocytosis and cytokine production, has been observed in human PBMCs exposed to the adjuvant and whole vaccines ( 43 ). Moreover, the ME3 module was mainly enriched in terms related to ER stress and the unfolded protein response (UPR) signaling cascade.…”

Section: Discussionmentioning

confidence: 99%

Identifying transcriptomic profiles in ovine spleen after repetitive vaccination

Guisasola-Serrano,

Bilbao-Arribas,

Varela-Martínez

et al. 2024

Front. Immunol.

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Aluminum hydroxide has long been employed as a vaccine adjuvant for its safety profile, although its precise mechanism of action remains elusive. In this study, we investigated the transcriptomic responses in sheep spleen following repetitive vaccination with aluminum adjuvanted vaccines and aluminum hydroxide alone. Notably, this work represents the first exploration of the sheep spleen transcriptome in such conditions. Animals were splitted in 3 treatment groups: vaccine group, adjuvant alone group and control group. A total of 18 high-depth RNA-seq libraries were sequenced, resulting in a rich dataset which also allowed isoform-level analysis. The comparisons between vaccine-treated and control groups (V vs C) as well as between vaccine-treated and adjuvant-alone groups (V vs A) revealed significant alterations in gene expression profiles, including protein coding genes and long non-coding RNAs. Among the differentially expressed genes, many were associated with processes such as endoplasmic reticulum (ER) stress, immune response and cell cycle. The analysis of co-expression modules further indicated a correlation between vaccine treatment and genes related to ER stress and unfolded protein response. Surprisingly, adjuvant-alone treatment had little impact on the spleen transcriptome. Additionally, the role of alternative splicing in the immune response was explored. We identified isoform switches in genes associated with immune regulation and inflammation, potentially influencing protein function. In conclusion, this study provides valuable insights into the transcriptomic changes in sheep spleen following vaccination with aluminum adjuvanted vaccines and aluminum hydroxide alone. These findings shed light on the molecular mechanisms underlying vaccine-induced immune responses and emphasize the significance of antigenic components in aluminum adjuvant mechanism of action. Furthermore, the analysis of alternative splicing revealed an additional layer of complexity in the immune response to vaccination in a livestock species.

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Advances on the early cellular events occurring upon exposure of human macrophages to aluminum oxyhydroxide adjuvant

Cited by 7 publications

References 62 publications

Mitochondrial Oxidative Stress Is the General Reason for Apoptosis Induced by Different-Valence Heavy Metals in Cells and Mitochondria

Mitochondrial Oxidative Stress Is the General Reason for Apoptosis Induced by Different-Valence Heavy Metals in Cells and Mitochondria

Adjuvanting Property of Aqueous Extract of the Indian Mistletoe, Dendrophthoe falcata

Identifying transcriptomic profiles in ovine spleen after repetitive vaccination

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