scholarly journals Maternal infection promotes offspring tissue-specific immune fitness

2021 ◽  
Author(s):  
Ai Ing Lim ◽  
Taryn McFadden ◽  
Verena M. Link ◽  
Seong-Ji Han ◽  
Rose-Marie Karlsson ◽  
...  
Keyword(s):  
Immune System ◽  
Epithelial Cells ◽  
Protective Immunity ◽  
Developmental Stages ◽  
Intestinal Epithelial ◽  
Maternal Infection ◽  
Tissue Specific ◽  
The Face ◽  
Mammalian Immune System

AbstractThe mammalian immune system has evolved in the face of microbial exposure. How maternal infection experienced at distinct developmental stages shapes the offspring immune system remains poorly understood. Here we show that during pregnancy, maternally restricted infection can have permanent and tissue-specific impacts on offspring immunity. Mechanistically, maternal IL-6 produced in response to infection can specifically and directly impose epigenetic changes on fetal intestinal epithelial cells. Such imprinting is associated with long-lasting impacts on intestinal immune homeostasis, characterized by enhanced tonic immunity to the microbiota and heightened Th17 responses within the gut, but not at other barrier sites. Furthermore, the offspring from IL-6-exposed dams developed enhanced protective immunity to gastrointestinal infection. Together, this work demonstrates that maternal infection experienced during pregnancy can be coopted by the fetus to promote long-term tissue-specific fitness.Summary sentenceInfection-induced maternal IL-6 impacts offspring epithelial cells, resulting in heightened immunity to the microbiota and pathogens.

scholarly journals Interleukin-7 Produced by Intestinal Epithelial Cells in Response to Citrobacter rodentium Infection Plays a Major Role in Innate Immunity against This Pathogen

2015 ◽  
Vol 83 (8) ◽  
pp. 3213-3223 ◽  
Author(s):  
Wei Zhang ◽  
Jiang-Yuan Du ◽  
Qing Yu ◽  
Jun-O Jin
Keyword(s):  
Epithelial Cells ◽  
Protective Immunity ◽  
Bacterial Infections ◽  
Intestinal Epithelial Cells ◽  
Intestinal Damage ◽  
Intestinal Epithelial ◽  
Citrobacter Rodentium ◽  
Content Type ◽  
Interleukin 7

Interleukin-7 (IL-7) engages multiple mechanisms to overcome chronic viral infections, but the role of IL-7 in bacterial infections, especially enteric bacterial infections, remains unclear. Here we characterized the previously unexplored role of IL-7 in the innate immune response to the attaching and effacing bacteriumCitrobacter rodentium.C. rodentiuminfection induced IL-7 production from intestinal epithelial cells (IECs). IL-7 production from IECs in response toC. rodentiumwas dependent on gamma interferon (IFN-γ)-producing NK1.1+cells and IL-12. Treatment with anti-IL-7Rα antibody duringC. rodentiuminfection resulted in a higher bacterial burden, enhanced intestinal damage, and greater weight loss and mortality than observed with the control IgG treatment. IEC-produced IL-7 was only essential for protective immunity againstC. rodentiumduring the first 6 days after infection. An impaired bacterial clearance upon IL-7Rα blockade was associated with a significant decrease in macrophage accumulation and activation in the colon. Moreover,C. rodentium-induced expansion and activation of intestinal CD4+lymphoid tissue inducer (LTi) cells was completely abrogated by IL-7Rα blockade. Collectively, these data demonstrate that IL-7 is produced by IECs in response toC. rodentiuminfection and plays a critical role in the protective immunity against this intestinal attaching and effacing bacterium.

scholarly journals LPA stimulates intestinal DRA gene transcription via LPA2 receptor, PI3K/AKT, and c-Fos-dependent pathway

2012 ◽  
Vol 302 (6) ◽  
pp. G618-G627 ◽  
Author(s):  
Amika Singla ◽  
Anoop Kumar ◽  
Shubha Priyamvada ◽  
Maliha Tahniyath ◽  
Seema Saksena ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Gene Transcription ◽  
Promoter Activity ◽  
Intestinal Epithelial Cells ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Intestinal Epithelial ◽  
Short Term ◽  
Exchange Activity

DRA (downregulated in adenoma) or SLC26A3 is the major apical anion exchanger mediating Cl− absorption in intestinal epithelial cells. Disturbances in DRA function and expression have been implicated in diarrheal conditions such as congenital chloride diarrhea and inflammatory bowel diseases. Previous studies have shown that DRA is subject to regulation by short-term and transcriptional mechanisms. In this regard, we have recently shown that short-term treatment by lysophosphatidic acid (LPA), an important bioactive phospholipid, stimulates Cl−/HCO3−(OH−) exchange activity via an increase in DRA surface levels in human intestinal epithelial cells. However, the long-term effects of LPA on DRA at the level of gene transcription have not been examined. The present studies were aimed at investigating the effects of LPA on DRA function and expression as well as elucidating the mechanisms underlying its transcriptional regulation. Long-term LPA treatment increased the Cl−/HCO3− exchange activity in Caco-2 cells. LPA treatment (50–100 μM) of Caco-2 cells significantly stimulated DRA mRNA levels and DRA promoter activity (−1183/+114). This increase in DRA promoter activity involved the LPA2 receptor and phosphatidylinositol 3-kinase (PI3K)/AKT pathways. Progressive deletions from −1183/+114 to −790/+114 abrogated the stimulatory effects of LPA, indicating that the −1183/−790 promoter region harbors LPA response elements. Utilizing EMSA and mutational studies, our results showed that LPA induced the DRA promoter activity in a c-Fos-dependent manner. LPA also increased the protein expression of c-Fos and c-Jun in Caco-2 cells. Furthermore, overexpression of c-Fos but not c-Jun enhanced the DRA promoter activity. This increase in DRA transcription in response to LPA indicates that LPA may act as an antidiarrheal agent and could be exploited for the treatment of diarrhea associated with inflammatory or infectious diseases of the gut.

Short- and long-term regulation of intestinal Na+/H+ exchange by Toll-like receptors TLR4 and TLR5

2015 ◽  
Vol 309 (8) ◽  
pp. G703-G715 ◽  
Author(s):  
José Miguel Cabral ◽  
Daniela Grácio ◽  
Patrício Soares-da-Silva ◽  
Fernando Magro
Keyword(s):  
Epithelial Cells ◽  
Lipid A ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Short Term ◽  
Monophosphoryl Lipid A ◽  
Nhe1 Activity ◽  
Short And Long Term ◽  
Tlr4 Activation

Inappropriate activation of pattern recognition receptors has been described as a potential trigger in the development of inflammatory bowel disease (IBD). In this study, we evaluated the activity and expression of Na+/H+ exchanger (NHE) subtypes in T84 intestinal epithelial cells during Toll-like receptor 4 (TLR4) activation by monophosphoryl lipid A and TLR5 by flagellin. NHE activity and intracellular pH were evaluated by spectrofluorescence. Additionally, kinase activities were evaluated by ELISA, and siRNA was used to specifically inhibit adenylyl cyclase (AC). Monophosphoryl lipid A (MPLA) (0.01–50.00 μg/ml) and flagellin (10–500 ng/ml) inhibited NHE1 activity in a concentration-dependent manner (MPLA short term −25.2 ± 5.0%, long term −31.9 ± 4.0%; flagellin short term −14.9 ± 2.0%, long term −19.1 ± 2.0%). Both ligands triggered AC3, PKA, PLC, and PKC signal molecules. Long-term exposure to flagellin and MPLA induced opposite changes on NHE3 activity; flagellin increased NHE3 activity (∼10%) with overexpression of membrane protein, whereas MPLA decreased NHE3 activity (−17.3 ± 3.0%). MPLA and flagellin simultaneously had synergistic effects on NHE activity. MPLA and flagellin impaired pHi recovery after intracellular acidification. The simultaneous exposure to MPLA and flagellin induced a substantial pHi reduction (−0.55 ± 0.03 pH units). Activation of TLR4 and TLR5 exerts marked inhibition of NHE1 activity in intestinal epithelial cells. Transduction mechanisms set into motion during TLR4-mediated and long-term TLR5-mediated inhibition of NHE1 activity involve AC3, PKA, PLC, and PKC. However, short- and long-term TLR4 activation and TLR5 activation might use different signaling pathways. The physiological alterations on intestinal epithelial cells described here may be useful in the development of better IBD therapeutics.

557 TNF-α-Induced Long-Term NF-κB Activation in Intestinal Epithelial Cells: Evidence for Autophagic Degradation of IκBα

2010 ◽  
Vol 138 (5) ◽  
pp. S-77
Author(s):  
Amy Colleran ◽  
Aideen E. Ryan ◽  
Angela Ogorman ◽  
Catherine H. Liptrot ◽  
Peter Dockery ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Tnf Α ◽  
Autophagic Degradation

scholarly journals Short‐ and Long‐term Regulation of Intestinal Na + /H + exchange by TLR4 in intestinal epithelial cells

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
Jose Cabral ◽  
Daniela Grácio ◽  
Patricio Soares‐da‐Silva ◽  
Fernando Magro
Keyword(s):  
Epithelial Cells ◽  
Intestinal Epithelial Cells ◽  
Intestinal Epithelial ◽  
Short And Long Term

Probiotic bacteria cell walls stimulate the activity of the intestinal epithelial cells and macrophage functionality

2018 ◽  
Vol 9 (1) ◽  
pp. 153-164 ◽  
Author(s):  
J.M. Lemme-Dumit ◽  
M.A. Polti ◽  
G. Perdigón ◽  
C. Maldonado Galdeano
Keyword(s):  
Immune System ◽  
Epithelial Cells ◽  
Oral Administration ◽  
Cell Walls ◽  
Intestinal Epithelial Cells ◽  
Immunoglobulin A ◽  
Mucosal Immune Response ◽  
Innate Immune ◽  
Probiotic Bacteria ◽  
Intestinal Epithelial

The effect of oral administration of probiotic bacteria cell walls (PBCWs) in the stimulation of the immune system in healthy BALB/c mice was evaluated. We focused our investigation mainly on intestinal epithelial cells (IECs) which are essential for coordinating an adequate mucosal immune response and on the functionality of macrophages. The probiotic bacteria and their cell walls were able to stimulate the IECs exhibiting an important activation and cytokine releases. Supplementation with PBCWs promoted macrophage activation from peritoneum and spleen, indicating that the PBCWs oral administration was able to improve the functionality of the macrophages. In addition, the PBCWs increased immunoglobulin A (IgA)-producing cells in the gut lamina propria in a similar way to probiotic bacteria, but this supplementation did not have an effect on the population of goblet cells in the small intestine epithelium. These results indicate that the probiotic bacteria and their cell walls have an important immunoregulatory effect on the IECs without altering the homeostatic environment but with an increase in IgA+ producing cells and in the innate immune cells, mainly those distant from the gut such as spleen and peritoneum. These findings about the capacity of the cell walls from probiotic bacteria to stimulate key cells, such as IECs and macrophages, and to improve the functioning of the immune system, suggest that those structures could be applied as a new oral adjuvant.

L-Threonine upregulates β-defensins expression by activating NF-κB signaling pathway and suppressing SIRT1 expression in porcine intestinal epithelial cells

2021 ◽  
Author(s):  
Chenxi Wang ◽  
Yang Yang ◽  
Nan Gao ◽  
Jing Lan ◽  
Xiujing Dou ◽  
...  
Keyword(s):  
Immune System ◽  
Epithelial Cells ◽  
Antimicrobial Peptide ◽  
Signaling Pathway ◽  
Innate Immune System ◽  
Intestinal Epithelial Cells ◽  
Innate Immune ◽  
Pivotal Role ◽  
Intestinal Epithelial ◽  
New Strategy

The use of antimicrobial peptide (AMP), found in all forms of life and playing a pivotal role in the innate immune system, has been developed as a new strategy for...

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