Homeostatic Immunity and the Microbiota

Belkaid, Yasmine; Harrison, Oliver J.

doi:10.1016/j.immuni.2017.04.008

Cited by 952 publications

(790 citation statements)

References 196 publications

(253 reference statements)

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“…1 , 2 Sustained shifts in gut microbiota composition are termed dysbiosis, which are often characterized by a lower phylogenetic diversity and an over- and/or under-representation of particular microbial taxa. In humans, dysbiosis is observed in multiple immune and metabolic diseases, including inflammatory bowel disease (IBD) and obesity.…”

Section: Need For Controlled Experimental Design When Evaluating Causmentioning

confidence: 99%

Inflammasomes make the case for littermate-controlled experimental design in studying host-microbiota interactions

et al. 2018

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Several human diseases are thought to evolve due to a combination of host genetic mutations and environmental factors that include alterations in intestinal microbiota composition termed dysbiosis. Although in some cases, host genetics may shape the gut microbiota and enable it to provoke disease, experimentally disentangling cause and consequence in such host-microbe interactions requires strict control over non-genetic confounding factors. Mouse genetic studies previously proposed Nlrp6/ASC inflammasomes as innate immunity regulators of the intestinal ecosystem. In contrast, using littermate-controlled experimental setups, we recently showed that Nlrp6/ASC inflammasomes do not alter the gut microbiota composition. Our analyses indicated that maternal inheritance and long-term separate housing are non-genetic confounders that preclude the use of non-littermate mice when analyzing host genetic effects on intestinal ecology. Here, we summarize and discuss our gut microbiota analyses in inflammasome-deficient mice for illustrating the importance of littermate experimental design in studying host-microbiota interactions.

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Section: Need For Controlled Experimental Design When Evaluating Causmentioning

confidence: 99%

Inflammasomes make the case for littermate-controlled experimental design in studying host-microbiota interactions

et al. 2018

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“…IgA maintains microbiota diversity and its compartmentalization. Loss of T H 17 cells and their protective functions are associated with bacterial translocation [8]. B cells also secrete IgA that regulates interactions of the host with the commensals and prevent their adhesion to the epithelial surfaces [8].…”

Section: Interaction Between the Gut Microbiota And The Host Immune Smentioning

confidence: 99%

The Gut Microbiota and Hematopoietic Stem Cell Transplantation: Challenges and Potentials

et al. 2018

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The human gut microbiota gained tremendous importance in the last decade as next-generation technologies of sequencing and multiomics analyses linked the role of the microbial communities to host physiology and pathophysiology. A growing number of human pathologies and diseases are linked to the gut microbiota. One of the main mechanisms by which the microbiota influences the host is through its interactions with the host immune system. These interactions with both innate and adaptive host intestinal and extraintestinal immunity, although usually commensalistic even mutualistic with the host, in some cases lead to serious health effects. In the case of allogenic hematopoietic stem cell transplantation (allo-HSCT), the disruption of the intestinal microbiota diversity is associated with acute graft-versus-host disease (GvHD). Causing inflammation of the liver, skin, lungs, and the intestine, GvHD occurs in 40–50% of patients undergoing allo-HSCT and results in significant posttransplantation mortality. In this review, we highlight the impact of the gut microbiota on the host immunity in GvHD and the potential of microbiota in alleviation or even prevention of GvHD.

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“…Immunosuppression refers to the attenuation of a healthy immune response toward antigens, either deliberately through administration of immunosuppressive drugs, or as an adverse effect of a therapeutic agent such as anti-neoplastic chemotherapy [1, 2]. Recently, anti-cancer immunity has been the focus of cancer research.…”

Section: Introductionmentioning

confidence: 99%

“…Recently, anti-cancer immunity has been the focus of cancer research. In general, the degree of tumor immunosuppression is determined by several factors including the ability of tumor cells to generate an immune-tolerant microenvironment, the activation of negative regulatory immune checkpoints in the tumor microenvironment and the secretion of immunosuppressive cytokines and soluble inhibitory factors [1, 2]. The tumor microenvironment is dictated mainly by the interaction between tumor cells and the immune system.…”

Section: Introductionmentioning

confidence: 99%

Plasminogen Activator Inhibitor 1 Promotes Immunosuppression in Human Non-Small Cell Lung Cancers by Enhancing TGF-Β1 Expression in Macrophage

Zhu¹,

Shen²,

Zhu³

et al. 2017

Cell Physiol Biochem

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Background: Plasminogen activator inhibitor-1 (PAI-1) has been regarded as a risk factor for thrombosis and atherosclerosis. Since it has been shown that PAI-1 can activate macrophages through Toll-like receptor-4, we sought to investigate the role of PAI-1 in the tumor microenvironment. Methods: The expression and distribution patterns of PAI-1 and transforming growth factor beta (TGF-β) were measured in 60 non-small cell lung cancer (NSCLC) tumors. A statistical correlation analysis was performed between PAI-1 and TGF-β expression and distribution in each tumor. The distribution of tumor-associated macrophages (TAMs) was also measured and its correlation to PAI-1 levels was analyzed. Levels of secreted CCL-17, CCL-22, IL-6 and TGF-β were measured in cell cultures of human macrophage cell lines THP-1 and U937 treated with PAI-1. Levels of secreted PAI-1 were monitored in cell cultures of human NSCLCs cell lines 95D and A549 treated with TGF-β. Secreted proteins were measured in cell culture supernatants using ELISA. Changes in downstream signaling pathways were investigated using western blot. Results: PAI-1 and TGF-β were found to be overexpressed in human NSCLCs. PAI-1 expression was tightly correlated to TGF-β expression as well as the percentage of TAMs. PAI-1 treatment increased the expression of TAM-associated cytokines and chemokines, including CCL-17, CCL-22, and IL-6. PAI-1 treatment was also observed to enhance TGF-β expression in macrophage cell lines through an IL-6 autocrine/paracrine manner. The effects on TGF-β expression were blocked by NF-κB and STAT3 inhibition. Interestingly, TGF-β also increased levels of secreted PAI-1 in NSCLC cells through SMAD3-dependent signaling, therefore resulting in a feed-forward loop. However, this loop could be blocked by NF-κB, STAT3 and SMAD3 signaling inhibition, as well as treatment with a high concentration of TGF-β. Conclusion: PAI-1 and TGF-β promote NSCLC tumor cells and TAMs and might be valuable targets for cancer immunosuppression.

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Homeostatic Immunity and the Microbiota

Cited by 952 publications

References 196 publications

Inflammasomes make the case for littermate-controlled experimental design in studying host-microbiota interactions

Inflammasomes make the case for littermate-controlled experimental design in studying host-microbiota interactions

The Gut Microbiota and Hematopoietic Stem Cell Transplantation: Challenges and Potentials

Plasminogen Activator Inhibitor 1 Promotes Immunosuppression in Human Non-Small Cell Lung Cancers by Enhancing TGF-Β1 Expression in Macrophage

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