The interaction of enteric bacterial effectors with the host engulfment pathway control innate immune responses

Sayed, Ibrahim M.; Ibeawuchi, Stella‐Rita; Lie, Dominique; Anandachar, Mahitha Shree; Pranadinata, Rama; Raffatellu, Manuela; Das, Soumita

doi:10.1080/19490976.2021.1991776

Cited by 13 publications

(54 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This result is consistent with previous studies. 37 , 44 , 47 , 93 These findings suggest that DSS could affect the relative abundance of intestinal microorganisms and the level of inflammatory factors in mice, disrupt intestinal immune balance, cause tissue damage and induce UC.…”

Section: Discussionmentioning

confidence: 96%

Dynamic Changes in Gut Microbiome of Ulcerative Colitis: Initial Study from Animal Model

Gu¹,

Zhang²,

Han³

et al. 2022

JIR

View full text Add to dashboard Cite

Background An animal model of DSS-induced UC has been widely used in basic research, and the dysbiosis of gut microbiome is one of the important pathogenetic mechanisms of DSS-induced UC, but its dynamic changes and correlation with inflammatory factors are not clear yet. Methods Clinical signs and tissue damage degree of C57BL/6 ulcerative colitis mice model induced by different concentrations of DSS were compared with that of normal mice, and finally the optimal concentration of DSS was determined. Then we analyzed the sequencing results of gut microbiome and inflammatory factors to determine the dynamic patterns of gut microbiome and their correlation with the inflammatory factors. Results DSS at 2.5% and 3.0% concentration could cause intestinal injury and induce colitis. However, 3.0% DSS resulted in higher mortality. In addition, there were dynamic changes of gut microbiome in DSS-induced UC model: the relative abundance of intestinal flora increased first and then decreased in Bacteroides , Parabacteroides , Romboutsia , Clostridium_sensu_stricto_1, Lachnospiraceae_NK4A136_group, norank_f_norank_o_Clostridia_UCG-014, Parasutterella , and decreased first and then increased in Lactobacillus , Muribaculum , norank_f_Muribaculaceae, in addition, Bifidobacterium , Coriobacteriaceae_UCG-002 and Enterorhabdus did not change in the first 14 days but increased significantly on day 21. Moreover, inflammatory cytokines were closely associated with the imbalance of the intestinal microbiota in mice with UC: most pathogenic bacteria in the intestinal tract of the UC animal model were positively correlated with pro-inflammatory factors and negatively correlated with anti-inflammatory factors, while beneficial bacteria were the opposite. Conclusion Intestinal microecology plays an important role in DSS-induced UC model, and the relative abundance of gut microbiome changes dynamically in the occurrence and development of ulcerative colitis.

show abstract

Section: Discussionmentioning

confidence: 96%

Dynamic Changes in Gut Microbiome of Ulcerative Colitis: Initial Study from Animal Model

Gu¹,

Zhang²,

Han³

et al. 2022

JIR

View full text Add to dashboard Cite

show abstract

“…We have shown previously that ELMO1 present in phagosome regulates bacterial clearance in macrophages 13,23 . Further, ELMO1 KO mice showed reduced colonic inflammation and pro-inflammatory cytokines following intestinal pathogen infection 9,26 . Here, we isolated bone marrow-derived macrophages (BMDM) from NOD2 KO mice to validate our findings in EDMs.…”

Section: Elmo1-nod2 Interaction Fine-tunes Paracellular Permeability ...mentioning

confidence: 99%

“…One such protein is EnguLfment and cell MOtility protein 1 (ELMO1), which has been recently implicated in having a role in microbial sensing. ELMO1 facilitates bacterial internalization, mounts inflammatory response, and coordinates bacterial clearance [6][7][8][9] . Brain Angiogenesis Inhibitor-1 (BAI1) recognizes bacterial lipopolysaccharide, interacts with ELMO1 resulting in the activation of Rac1 and induction of proinflammatory cytokines 10 .…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

“…Using enteroid-derived monolayers (EDMs) from the organoids isolated from colonic biopsies of IBD patients, we have demonstrated that bacterial internalization and production of proinflammatory cytokines such as TNF-α and MCP-1 are ELMO1-dependent, which consequently triggers the chronic inflammatory cascade of IBD 11 . Interestingly, we found that ELMO1 induces differential immune responses between pathogens and commensals by interacting with several bacterial effectors containing the WxxxE motif 9 NOD2 is a cytosolic PRR belonging to the Nod-like receptor (NLR) family that recognizes processed bacterial cell wall component, muramyl dipeptide (MDP), from both Gram-positive and Gram-negative bacteria 12 . NOD2 activation results in recruitment of RICK (RIP-like interacting CLARP kinase)/RIP2 (Receptor-Interacting Protein 2) and activation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The crosstalk between microbial sensors ELMO1 and NOD2 shape intestinal immune responses

Sharma

Achi

Ibeawuchi

et al. 2022

Preprint

Self Cite

View full text Add to dashboard Cite

Microbial sensors play an essential role in maintaining cellular homeostasis. Our knowledge is limited on how microbial sensing helps in differential immune response and its link to inflammatory diseases. Recently, we have shown that cytosolic sensor ELMO1 (Engulfment and Cell Motility Protein-1) binds to effectors from pathogenic bacteria and controls intestinal inflammation. Here, we show that ELMO1 interacts with another sensor, NOD2 (Nucleotide-binding oligomerization domain-containing protein 2), that recognizes bacterial cell wall component muramyl dipeptide (MDP). The polymorphism of NOD2 is linked to Crohns disease (CD) pathogenesis. Interestingly, we found that overexpression of ELMO1 and mutant NOD2 (L1007fs) were not able to clear the CD-associated adherent invasive E. coli (AIEC-LF82). To understand the interplay of microbial sensing of ELMO1-NOD2 in epithelial cells and macrophages, we used enteroid-derived monolayers (EDMs) from ELMO1 and NOD2 KO mice and ELMO1 and NOD2-depleted murine macrophage cell lines. The infection of murine EDMs with AIEC-LF82 showed higher bacterial load in ELMO1-KO, NOD2 KO EDMs, and ELMO1 KO EDMs treated with NOD2 inhibitors. The murine macrophage cells showed that the downregulation of ELMO1 and NOD2 is associated with impaired bacterial clearance that is linked to reduced pro-inflammatory cytokines and reactive oxygen species. Our results indicated that the crosstalk between microbial sensors in enteric infection and inflammatory diseases impacts the fate of the bacterial load and disease pathogenesis.

show abstract

The triangular relationship between traditional Chinese medicines, intestinal flora, and colorectal cancer

Zou,

Wang,

Zhang

et al. 2023

Medicinal Research Reviews

View full text Add to dashboard Cite

Over the past decade, colorectal cancer has reported a higher incidence in younger adults and a lower mortality rate. Recently, the influence of the intestinal flora in the initiation, progression, and treatment of colorectal cancer has been extensively studied, as well as their positive therapeutic impact on inflammation and the cancer microenvironment. Historically, traditional Chinese medicine (TCM) has been widely used in the treatment of colorectal cancer via promoted cancer cell apoptosis, inhibited cancer metastasis, and reduced drug resistance and side effects. The present research is more on the effect of either herbal medicine or intestinal flora on colorectal cancer. The interactions between TCM and intestinal flora are bidirectional and the combined impacts of TCM and gut microbiota in the treatment of colon cancer should not be neglected. Therefore, this review discusses the role of intestinal bacteria in the progression and treatment of colorectal cancer by inhibiting carcinogenesis, participating in therapy, and assisting in healing. Then the complex anticolon cancer effects of different kinds of TCM monomers, TCM drug pairs, and traditional Chinese prescriptions embodied in apoptosis, metastasis, immune suppression, and drug resistance are summarized separately. In addition, the interaction between TCM and intestinal flora and the combined effect on cancer treatment were analyzed. This review provides a mechanistic reference for the application of TCM and intestinal flora in the clinical treatment of colorectal cancer and paves the way for the combined development and application of microbiome and TCM.

show abstract

The interaction of enteric bacterial effectors with the host engulfment pathway control innate immune responses

Cited by 13 publications

References 49 publications

Dynamic Changes in Gut Microbiome of Ulcerative Colitis: Initial Study from Animal Model

Dynamic Changes in Gut Microbiome of Ulcerative Colitis: Initial Study from Animal Model

The crosstalk between microbial sensors ELMO1 and NOD2 shape intestinal immune responses

The triangular relationship between traditional Chinese medicines, intestinal flora, and colorectal cancer

Contact Info

Product

Resources

About