Endotoxin tolerance and trained immunity: breaking down immunological memory barriers

López-Collazo, Eduardo; del Fresno, Carlos

doi:10.3389/fimmu.2024.1393283

Cited by 2 publications

(1 citation statement)

References 162 publications

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“…When the phenomenon endotoxin tolerance was introduced, the focus was largely on how treatments with low doses of LPS could prevent lethal outcomes of sepsis and fever. A broader understanding of endotoxin tolerance has been revealed through studies of possible beneficial mechanisms in areas of various chronic inflammatory diseases ( 60 , 61 ) and other more specific areas such as cancer immunotherapy ( 58 , 62 ). Endotoxin tolerance can be divided into early and late mechanisms of tolerance.…”

Section: Discussionmentioning

confidence: 99%

Chronic oral LPS administration does not increase inflammation or induce metabolic dysregulation in mice fed a western-style diet

Harvei,

Skogen,

Egelandsdal

et al. 2024

Front. Nutr.

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IntroductionLipopolysaccharides (LPS) present in the intestine are suggested to enter the bloodstream after consumption of high-fat diets and cause systemic inflammation and metabolic dysregulation through a process named “metabolic endotoxemia.” This study aimed to determine the role of orally administered LPS to mice in the early stage of chronic low-grade inflammation induced by diet.MethodsWe supplemented the drinking water with E. coli derived LPS to mice fed either high-fat Western-style diet (WSD) or standard chow (SC) for 7 weeks (n = 16–17). Body weight was recorded weekly. Systemic inflammatory status was assessed by in vivo imaging of NF-κB activity at different time points, and glucose dysregulation was assessed by insulin sensitivity test and glucose tolerance test near the end of the study. Systemic LPS exposure was estimated indirectly via quantification of LPS-binding protein (LBP) and antibodies against LPS in plasma, and directly using an LPS-sensitive cell reporter assay.Results and discussionOur results demonstrate that weight development and glucose regulation are not affected by LPS. We observed a transient LPS dependent upregulation of NF-κB activity in the liver region in both diet groups, a response that disappeared within the first week of LPS administration and remained low during the rest of the study. However, WSD fed mice had overall a higher NF-κB activity compared to SC fed mice at all time points independent of LPS administration. Our findings indicate that orally administered LPS has limited to no impact on systemic inflammation and metabolic dysregulation in mice fed a high-fat western diet and we question the capability of intestinally derived LPS to initiate systemic inflammation through a healthy and uncompromised intestine, even when exposed to a high-fat diet.

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Section: Discussionmentioning

confidence: 99%

Chronic oral LPS administration does not increase inflammation or induce metabolic dysregulation in mice fed a western-style diet

Harvei,

Skogen,

Egelandsdal

et al. 2024

Front. Nutr.

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Hypothesis: hematogenous metastatic cancer cells of solid tumors may disguise themselves as memory macrophages for metastasis

Jiang,

2024

Front. Oncol.

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German pathologist Otto Aichel suggested, a century ago, that the cancer cell acquired its metastatic property from a leukocyte via cell-cell fusion. Since then, several revised versions of this theory have been proposed. Most of the proposals attribute the generation of the metastatic cancer cell to the fusion between a primary cancer cell and a macrophage. However, these theories have not addressed several issues, such as dormancy and stem cell-like self-renewal, of the metastatic cancer cell. On the other hand, recent studies have found that, like T- and B-/plasma cells, macrophages can also be categorized into naïve, effector, and memory/trained macrophages. As a memory/trained macrophage can enter dormancy/quiescence, be awakened from the dormancy/quiescence by acquainted primers, and re-populate via stem cell-like self-renewal, we, therefore, further specify that the macrophage fusing with the cancer cell and contributing to metastasis, belongs with the memory/trained macrophage, not other subtypes of macrophages. The current theory can explain many puzzling clinical features of cancer, including the paradoxal effects (recurrence vs. regression) of microbes on tumors, “spontaneous” and Coley’s toxin-induced tumor regression, anticancer activities of β-blockers and anti-inflammatory/anti-immune/antibiotic drugs, oncotaxis, surgery- and trauma-promoted metastasis, and impact of microbiota on tumors. Potential therapeutic strategies, such as Coley’s toxin-like preparations, are proposed. This is the last article of our trilogy on carcinogenesis theories.

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Endotoxin tolerance and trained immunity: breaking down immunological memory barriers

Cited by 2 publications

References 162 publications

Chronic oral LPS administration does not increase inflammation or induce metabolic dysregulation in mice fed a western-style diet

Chronic oral LPS administration does not increase inflammation or induce metabolic dysregulation in mice fed a western-style diet

Hypothesis: hematogenous metastatic cancer cells of solid tumors may disguise themselves as memory macrophages for metastasis

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