scholarly journals Gastrointestinal epithelial innate immunity—regionalization and organoids as new model

2021 ◽  
Vol 99 (4) ◽  
pp. 517-530 ◽  
Author(s):  
Özge Kayisoglu ◽  
Nicolas Schlegel ◽  
Sina Bartfeld

AbstractThe human gastrointestinal tract is in constant contact with microbial stimuli. Its barriers have to ensure co-existence with the commensal bacteria, while enabling surveillance of intruding pathogens. At the centre of the interaction lies the epithelial layer, which marks the boundaries of the body. It is equipped with a multitude of different innate immune sensors, such as Toll-like receptors, to mount inflammatory responses to microbes. Dysfunction of this intricate system results in inflammation-associated pathologies, such as inflammatory bowel disease. However, the complexity of the cellular interactions, their molecular basis and their development remains poorly understood. In recent years, stem cell–derived organoids have gained increasing attention as promising models for both development and a broad range of pathologies, including infectious diseases. In addition, organoids enable the study of epithelial innate immunity in vitro. In this review, we focus on the gastrointestinal epithelial barrier and its regional organization to discuss innate immune sensing and development.

Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 567
Author(s):  
Renate König ◽  
Carsten Münk

In this Special Issue, a wide variety of original and review articles provide a timely overview of how viruses are recognized by and evade from cellular innate immunity, which represents the first line of defense against viruses [...]


2018 ◽  
Author(s):  
Priya Hari ◽  
Fraser R. Millar ◽  
Nuria Tarrats ◽  
Jodie Birch ◽  
Curtis J. Rink ◽  
...  

ABSTRACTCellular senescence is a stress response program characterised by a robust cell cycle arrest and the induction of a pro-inflammatory senescence-associated secretory phenotype (SASP) that is triggered through an unknown mechanism. Here, we show that during oncogene-induced senescence (OIS), the Toll-like receptor TLR2 and its partner TLR10 are key mediators of senescence in vitro and in murine models. TLR2 promotes cell cycle arrest by regulating the tumour suppressors p53-p21CIP1, p16INK4a and p15INK4b, and regulates the SASP through the induction of the acute-phase serum amyloids A1 and A2 (A-SAA) that, in turn, function as the damage associated molecular patterns (DAMPs) signalling through TLR2 in OIS. Finally, we found evidence that the cGAS-STING cytosolic DNA sensing pathway primes TLR2 and A-SAA expression in OIS. In summary, we report that innate immune sensing of senescence-associated DAMPs by TLR2 controls the SASP and reinforces the cell cycle arrest program in OIS.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Augusto Schneider ◽  
Hillary N. Wood ◽  
Sandra Geden ◽  
Catherine J. Greene ◽  
Robin M. Yates ◽  
...  

AbstractMacrophages are an important component of the innate immune response. Priming and activation of macrophages is stimulated by cytokines (i.e IFNγ). However, growth hormone (GH) can also stimulate macrophage activation. Based on these observations, the goal of this work was to 1) to compare the transcriptome profile of macrophages activated in vitro with GH and IFNγ, and 2) to assess the impact of GH on key macrophage functional properties like reactive oxygen species (ROS) production and phagosomal proteolysis. To assess the global transcriptional and functional impact of GH on macrophage programming, bone marrow derived macrophages were treated with GH or IFNγ. Our data strongly support a potential link between GH, which wanes with age, and impaired macrophage function. The notable overlap of GH with IFNγ-induced pathways involved in innate immune sensing of pathogens and antimicrobial responses argue for an important role for GH in macrophage priming and maturation. By using functional assays that report on biochemical activities within the lumen of phagosomes, we have also shown that GH alters physiologically relevant processes such as ROS production and proteolysis. These changes could have far reaching impacts on antimicrobial capacity, signaling, and antigen presentation.


Vaccines ◽  
2021 ◽  
Vol 9 (7) ◽  
pp. 758
Author(s):  
Fiona Ingrao ◽  
Victoria Duchatel ◽  
Isabel Fernandez Rodil ◽  
Mieke Steensels ◽  
Eveline Verleysen ◽  
...  

Recombinant Newcastle disease viruses (rNDV) have been used as bivalent vectors for vaccination against multiple economically important avian pathogens. NDV-vectored vaccines expressing the immunogenic H5 hemagglutinin (rNDV-H5) are considered attractive candidates to protect poultry from both highly pathogenic avian influenza (HPAI) and Newcastle disease (ND). However, the impact of the insertion of a recombinant protein, such as H5, on the biological characteristics of the parental NDV strain has been little investigated to date. The present study compared a rNDV-H5 vaccine and its parental NDV LaSota strain in terms of their structural and functional characteristics, as well as their recognition by the innate immune sensors. Structural analysis of the rNDV-H5 demonstrated a decreased number of fusion (F) and a higher number of hemagglutinin-neuraminidase (HN) glycoproteins compared to NDV LaSota. These structural differences were accompanied by increased hemagglutinating and neuraminidase activities of rNDV-H5. During in vitro rNDV-H5 infection, increased mRNA expression of TLR3, TLR7, MDA5, and LGP2 was observed, suggesting that the recombinant virus is recognized differently by sensors of innate immunity when compared with the parental NDV LaSota. Given the growing interest in using NDV as a vector against human and animal diseases, these data highlight the importance of thoroughly understanding the recombinant vaccines’ structural organization, functional characteristics, and elicited immune responses.


2013 ◽  
Vol 2013 ◽  
pp. 1-13 ◽  
Author(s):  
Marina García-Miguel ◽  
M. Julieta González ◽  
Rodrigo Quera ◽  
Marcela A. Hermoso

Innate immunity prevents pathogens from entering and spreading within the body. This function is especially important in the gastrointestinal tract and skin, as these organs have a large surface contact area with the outside environment. In the intestine, luminal commensal bacteria are necessary for adequate food digestion and play a crucial role in tolerance to benign antigens. Immune system damage can create an intestinal inflammatory response, leading to chronic disease including inflammatory bowel diseases (IBD). Ulcerative colitis (UC) is an IBD of unknown etiology with increasing worldwide prevalence. In the intestinal mucosa of UC patients, there is an imbalance in the IL-33/ST2 axis, an important modulator of the innate immune response. This paper reviews the role of the IL-33/ST2 system in innate immunity of the intestinal mucosa and its importance in inflammatory bowel diseases, especially ulcerative colitis.


2020 ◽  
Author(s):  
Xiao-Ting Zhang ◽  
Yong-Yao Yu ◽  
Hao-Yue Xu ◽  
Zhen-Yu Huang ◽  
Xia Liu ◽  
...  

AbstractThe skin of vertebrates is the outermost organ of the body and serves as the first line of defense against external aggressions. In contrast to mammalian skin, that of teleost fish lacks keratinization and has evolved to operate as a mucosal surface containing a skin-associated lymphoid tissue (SALT). Thus far, IgT representing the prevalent immunoglobulin (Ig) in SALT have only been reported upon infection with a parasite. However, very little is known about the types of B cells and Igs responding to bacterial infection in the teleost skin mucosa, as well as the inductive or effector role of the SALT in such responses. To address these questions, here we analyzed the immune response of trout skin upon infection with one of the most widespread fish skin bacterial pathogens, Flavobacterium columnare. This pathogen induced strong skin innate immune and inflammatory responses at the initial phases of infection. More critically, we found that the skin mucus of fish having survived the infection contained significant IgT-but not IgM- or IgD-specific titers against the bacteria. Moreover, we demonstrate the local proliferation and production of IgT+ B-cells and specific IgT titers respectively within the SALT upon bacterial infection. Thus, our findings represent the first demonstration that IgT is the main Ig isotype induced by the skin mucosa upon bacterial infection, and that because of the large surface of the skin, its SALT probably represents a prominent IgT inductive site in fish.


Sign in / Sign up

Export Citation Format

Share Document