Human monocytes downregulate innate response receptors following exposure to the microbial metabolite n‐butyrate

Lasitschka, Felix; Giese, Thomas; Paparella, Marco; Kurzhals, Stefan R.; Wabnitz, Guido H.; Jacob, Katrin; Gras, Judith; Bode, Konrad A.; Heninger, Anne-Kristin; Sziskzai, Timea; Samstag, Yvonne; Leszinski, Cornelia; Jocher, Bettina; Al-Saeedi, Mohammed; Meuer, Stefan; Schröder‐Braunstein, Jutta

doi:10.1002/iid3.184

Cited by 20 publications

(12 citation statements)

References 86 publications

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“…Specifically, during monocyte-macrophage differentiation in the intestine, the expression of TFs early growth response gene (Egr1, 2, and 3) were upregulated while expression of C/EBP and E2F family members were significantly downregulated. together with TFs involved in regulating the immune response, such as Bach1, Bcl6, Irf9, Nfatc3, NfKb1, consistent with the hyporesponsive phenotype of intestinal macrophages [61]. In addition, consistent with past reports, the expression of Spi1 (PU.1) was also downregulated in these intestinal macrophages.…”

Section: Trends In Immunologysupporting

confidence: 89%

Monocyte Regulation in Homeostasis and Malignancy

Robinson

Han

Glass

et al. 2021

Trends in Immunology

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Monocytes are progenitors to macrophages and a subclass of dendritic cells (monocyte-derived dendritic cells, MoDCs), but they also act as circulating sensors that respond to environmental changes and disease. Technological advances have defined the production of classical monocytes in the bone marrow through the identification of lineage-determining transcription factors (LDTFs) and have proposed alternative routes of differentiation. Monocytes released into the circulation can be recruited to tissues by specific chemoattractants where they respond to sequential niche-specific signals that determine their differentiation into terminal effector cells. New aspects of monocyte biology in the circulation are being revealed, exemplified by the influence of cancer on the systemic alteration of monocyte subset abundance and transcriptional profiles. These changes can act to enhance the metastatic spread of primary cancers and may offer therapeutic opportunities. Monocytes: Key Players in the Innate Immune SystemThere are two major populations of monocytes in mouse and humans that have been termed classical and non-classical (see Glossary)as defined by specific markers (Table 1, Key Table ) as well as by an intermediate transitional population between classical and non-classical monocytes. During homeostasis, monocytes survey the vasculature or are recruited to continuously replenish tissue-resident macrophages (TRMs), for example in the gut. In response to inflammation, infection, or tissue damage, immune cell recruitment results in the development of effector macrophages that repel pathogens and mediate tissue repair (Figure 1 and Table 1) as well as a subclass of dendritic cells (MoDCs) [1]. Traditionally, monocytes have been primarily viewed as 'conduits' to processes involving macrophages or dendritic cells (DCs), and as being beneficial to the mammalian host. However, the frequency, activity, and fate of monocyte populations has also been linked to many diseases, including autoimmunity, chronic inflammation, cardiovascular disease, and cancer [2,3]. In these diseases, and others involving monocyte trafficking, environmental cues acting in the bone, blood, and tissues dynamically modify the transcriptional landscape of monocytes, resulting in phenotypes that can potentiate disease severity (Figure 1 and Table 1). Using the processes of monocyte development, we discuss the mechanisms of monocyte ontogeny, transcriptional regulation, and their relevance to tissue homeostasis. We also use cancer as an example of a disease state that can influence monocyte biology. We posit that a better understanding of this regulation is important because it might contribute to advancing monocyte-targeted therapies in cancer and in turn be potentially applicable to other progressive diseases. Mammalian Monocyte OntogenyMonocyte Development in Bone Postnatal monocytes are formed primarily in the bone marrow (BM) from the differentiation of hematopoietic stem cells (HSCs) into the common myeloid progenitor (CMP) cells, and subsequently...

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Section: Trends In Immunologysupporting

confidence: 89%

Monocyte Regulation in Homeostasis and Malignancy

Robinson

Han

Glass

et al. 2021

Trends in Immunology

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“…The Inf-ObMB mice showed a significant elevation in all three measured SCFAs in the gut, similar to changes noted in the infant donor stool 24 . Butyrate induces a hypo-responsive inflammatory state in macrophages through its action as an HDAC inhibitor 52 , 55 and can also interfere with macrophage differentiation, maturation, and the ability of macrophages to prime other arms of the innate and adaptive immune systems 56 . Although we did not measure butyrate in circulation, based on our data showing increased butyrate in the intestine, reduction in gut barrier integrity, and BMDM desensitization, we hypothesize that increased butyrate production by the infant gut dampens BMDM responsiveness to LPS 52 , 55 .…”

Section: Discussionmentioning

confidence: 99%

The gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD

et al. 2018

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Maternal obesity is associated with increased risk for offspring obesity and non-alcoholic fatty liver disease (NAFLD), but the causal drivers of this association are unclear. Early colonization of the infant gut by microbes plays a critical role in establishing immunity and metabolic function. Here, we compare germ-free mice colonized with stool microbes (MB) from 2-week-old infants born to obese (Inf-ObMB) or normal-weight (Inf-NWMB) mothers. Inf-ObMB-colonized mice demonstrate increased hepatic gene expression for endoplasmic reticulum stress and innate immunity together with histological signs of periportal inflammation, a histological pattern more commonly reported in pediatric cases of NAFLD. Inf-ObMB mice show increased intestinal permeability, reduced macrophage phagocytosis, and dampened cytokine production suggestive of impaired macrophage function. Furthermore, exposure to a Western-style diet in Inf-ObMB mice promotes excess weight gain and accelerates NAFLD. Overall, these results provide functional evidence supporting a causative role of maternal obesity-associated infant dysbiosis in childhood obesity and NAFLD.

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“…Though the exact mechanisms leading to the anti‐inflammatory effects of dietary Goji berry remain to be established, the elevation of butyrate might have an important role . As a major gut microbiota metabolite, butyrate is known to have strong anti‐inflammatory effects . Butyrate inhibits inflammatory signaling in immune cells, facilitates epithelial differentiation, and inhibits proliferation, as well as the assembly of tight junction complexes to strengthen epithelial barrier .…”

Section: Disscussionmentioning

confidence: 99%

Goji Berry Modulates Gut Microbiota and Alleviates Colitis in IL‐10‐Deficient Mice

Kang

Yang

Zhang

et al. 2018

Molecular Nutrition Food Res

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Scope This study examines the beneficial effects of Goji berry against spontaneous colitis and its prebiotic role in IL‐10‐deficient mice. Methods IL‐10‐deficient mice are assigned to a standard rodent diet (control) or a control diet supplemented with Goji (1% of dry feed weight) for 10 weeks, at which point colonic tissues and fecal contents are collected. Results Goji supplementation decreases colonic pathobiological scores and mRNA expression of Il17a and Tgfb1, while it enhances Muc1 expression and fecal IgA content. Illumina MiSeq sequencing reveals that Goji supplementation increases Actinobacteria phylum, resulting in a bloom of Bifidobacteria in gut microbiota. Additionally, dietary Goji promotes butyrate‐producing bacteria including Lachnospiraceae‐Ruminococcaceae family and Roseburia spp. under Clostridium cluster XIVa. Furthermore, butyrate‐producers Clostridium leptum and its dominant constituent Fecalibacterium prazusnitzii are markedly increased in the Goji group. Moreover, the gene‐encoding butyryl‐coenzyme A CoA transferase, a key enzyme responsible for butyrate synthesis in butyrate‐producing bacteria, is increased sixfold in the fecal samples of Goji group associated with increased fecal butyrate content. Conclusion Data collectively show that dietary Goji results in the blooming of Bifidobacteria and butyrate‐producing bacteria. These bacteria may cross‐feed each other, conferring preventative effects against colitis in IL‐10‐deficient mice.

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Human monocytes downregulate innate response receptors following exposure to the microbial metabolite n‐butyrate

Cited by 20 publications

References 86 publications

Monocyte Regulation in Homeostasis and Malignancy

Monocyte Regulation in Homeostasis and Malignancy

The gut microbiota in infants of obese mothers increases inflammation and susceptibility to NAFLD

Goji Berry Modulates Gut Microbiota and Alleviates Colitis in IL‐10‐Deficient Mice

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