scholarly journals The Role of Hyaluronan in Innate Defense Responses of the Intestine

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Carol A. de la Motte ◽  
Sean P. Kessler

Hyaluronan is an abundant extracellular matrix component prevalent in the vertebrate intestinal tract. Here we discuss what is known about hyaluronan distribution during homeostasis and inflammatory diseases of the gut and discuss ways in which this glycosaminoglycan can participate in regulating innate host defense mechanisms. These natural responses include mechanisms promoting rapid leukocyte recruitment after bacterial challenge/colon tissue damage as well as promoting epithelial defense mechanisms in the intestine.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
S. Duboux ◽  
M. Golliard ◽  
J. A. Muller ◽  
G. Bergonzelli ◽  
C. J. Bolten ◽  
...  

AbstractThe Serine Protease Inhibitor (serpin) protein has been suggested to play a key role in the interaction of bifidobacteria with the host. By inhibiting intestinal serine proteases, it might allow bifidobacteria to reside in specific gut niches. In inflammatory diseases where serine proteases contribute to the innate defense mechanism of the host, serpin may dampen the damaging effects of inflammation. In view of the beneficial roles of this protein, it is important to understand how its production is regulated. Here we demonstrate that Bifidobacterium longum NCC 2705 serpin production is tightly regulated by carbohydrates. Galactose and fructose increase the production of this protein while glucose prevents it, suggesting the involvement of catabolite repression. We identified that di- and oligosaccharides containing galactose (GOS) and fructose (FOS) moieties, including the human milk oligosaccharide Lacto-N-tetraose (LNT), are able to activate serpin production. Moreover, we show that the carbohydrate mediated regulation is conserved within B. longum subsp. longum strains but not in other bifidobacterial taxons harboring the serpin coding gene, highlighting that the serpin regulation circuits are not only species- but also subspecies- specific. Our work demonstrates that environmental conditions can modulate expression of an important effector molecule of B. longum, having potential important implications for probiotic manufacturing and supporting the postulated role of serpin in the ability of bifidobacteria to colonize the intestinal tract.


2020 ◽  
Author(s):  
Stéphane Duboux ◽  
Mireille Golliard ◽  
Jeroen Muller ◽  
Gabriela Bergonzelli ◽  
Christoph Bolten ◽  
...  

Abstract The Serine Protease Inhibitor (serpin) protein has been suggested to play a key role in the interaction of bifidobacteria with the host. By inhibiting intestinal serine proteases, it might allow bifidobacteria to reside in specific gut niches. In inflammatory diseases where serine proteases contribute to the innate defense mechanism of the host, serpin may dampen the damaging effects of inflammation. In view of the beneficial roles of this protein, it is important to understand how its production is regulated. Here we demonstrate that B. longum NCC 2705 serpin production is tightly regulated by carbohydrates. Galactose and fructose increase the production of this protein while glucose prevents it, suggesting the involvement of catabolite repression. We identified that di- and oligosaccharides containing galactose (GOS) and fructose (FOS) moieties, including the human milk oligosaccharide Lacto-N-tetraose (LNT), are able to activate serpin production. Moreover, we show that the carbohydrate mediated regulation is conserved within B. longum subsp. longum strains but not in other bifidobacterial taxons harboring the serpin coding gene, highlighting that the serpin regulation circuits are not only species- but also subspecies- specific. Our work demonstrates that environmental conditions can modulate expression of an important effector molecule of B. longum, having potential important implications for probiotic manufacturing and supporting the postulated role of serpin in the ability of bifidobacteria to colonize the intestinal tract.


2022 ◽  
Vol 15 ◽  
Author(s):  
Kaoru Isa ◽  
Kota Tokuoka ◽  
Sakura Ikeda ◽  
Sara Karimi ◽  
Kenta Kobayashi ◽  
...  

In our previous study, we showed that the defense responses induced by the selective optogenetic activation of the uncrossed output pathway from the deeper layer of the superior colliculus were environment dependent in the mouse. In a small closed box, the stimulus frequently induced flight (fast forward run away) responses, while in a large open field, the stimulus tended to induce backward retreat responses. We tested a hypothesis that the amygdala is involved in such environment dependency of the innate defense responses. For this purpose, we made a bilateral lesion of the amygdala induced by the ibotenic acid injections in male mice. As a result, in the mice with lesions of substantial portions of the basolateral and basomedial complex, the flight responses in the closed box disappeared and retreat responses were mainly induced. The retreat responses on the open platform were unchanged. Classically, the amygdala has been considered to be involved in the memory-dependent contextual modulation of the fear responses. In contrast, the present results suggest a novel view on the role of the amygdala in which the amygdala plays a key role in sensing the current environmental setting for making a quick decision of action upon emergency, which is critical for survival in the natural environment.


2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
C. Rodríguez-Cerdeira ◽  
A. Lopez-Bárcenas ◽  
B. Sánchez-Blanco ◽  
R. Arenas

Background. Interleukin (IL) 33 is a recently identified pleiotropic cytokine that influences the activity of multiple cell types and orchestrates complex innate and adaptive immune responses.Methods. We performed an extensive review of the literature published between 2005 and 2013 on IL-33 and related cytokines, their functions, and their regulation of the immune system followingCandida albicanscolonization. Our literature review included cross-references from retrieved articles and specific data from our own studies.Results. IL-33 (IL-1F11) is a recently identified member of the IL-1 family of cytokines. Accumulating evidence suggests a pivotal role of the IL-33/ST2 axis in host immune defense against fungal pathogens, includingC. albicans. IL-33 induces a Th2-type inflammatory response and activates both innate and adaptive immunity. Studies in animal models have shown that Th2 inflammatory responses have a beneficial role in immunity against gastrointestinal and systemic infections byCandidaspp.Conclusions. This review summarizes the most important clinical studies and case reports describing the beneficial role of IL-33 in immunity and host defense mechanisms against pathogenic fungi. The finding that the IL-33/ST2 axis is involved in therapeutic target has implications for the prevention and treatment of inflammatory diseases, including acute or chronic candidiasis.


Author(s):  
Imen Jridi ◽  
Kirsten Canté-Barrett ◽  
Karin Pike-Overzet ◽  
Frank J. T. Staal

Wnt proteins comprise a large family of highly conserved glycoproteins known for their role in development, cell fate specification, tissue regeneration, and tissue homeostasis. Aberrant Wnt signaling is linked to developmental defects, malignant transformation, and carcinogenesis as well as to inflammation. Mounting evidence from recent research suggests that a dysregulated activation of Wnt signaling is involved in the pathogenesis of chronic inflammatory diseases, such as neuroinflammation, cancer-mediated inflammation, and metabolic inflammatory diseases. Recent findings highlight the role of Wnt in the modulation of inflammatory cytokine production, such as NF-kB signaling and in innate defense mechanisms as well as in the bridging of innate and adaptive immunity. This sparked the development of novel therapeutic treatments against inflammatory diseases based on Wnt modulation. Here, we summarize the role and function of the Wnt pathway in inflammatory diseases and focus on Wnt signaling as underlying master regulator of inflammation that can be therapeutically targeted.


Animals ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 2330
Author(s):  
Kacper Libera ◽  
Kacper Konieczny ◽  
Katarzyna Witkowska ◽  
Katarzyna Żurek ◽  
Małgorzata Szumacher-Strabel ◽  
...  

The aim of this paper is to describe the association between selected dietary minerals and mastitis in dairy cows. Minerals are a group of nutrients with a proven effect on production and reproductive performance. They also strongly affect immune system function. In particular their deficiencies may result in immunosuppression, which is a predisposing factor for udder inflammation occurrence. The role of selected dietary minerals (including calcium, phosphorus, magnesium, selenium, copper and zinc) has been reviewed. Generally, minerals form structural parts of the body; as cofactors of various enzymes they are involved in nerve signaling, muscle contraction and proper keratosis. Their deficiencies lead to reduced activity of immune cells or malfunction of teat innate defense mechanisms, which in turn promote the development of mastitis. Special attention was also paid to minerals applied as nanoparticles, which in the future may turn out to be an effective tool against animal diseases, including mastitis. To conclude, minerals are an important group of nutrients, which should be taken into account on dairy farms when aiming to achieve high udder health status.


2014 ◽  
Vol 91 (3) ◽  
pp. 618-634 ◽  
Author(s):  
Simon Houston ◽  
Shannon Russell ◽  
Rebecca Hof ◽  
Alanna K. Roberts ◽  
Paul Cullen ◽  
...  

1984 ◽  
Vol 4 (1) ◽  
pp. 1-7 ◽  
Author(s):  
C C Howe

Previous work showed that tunicamycin suppresses glycosylation of laminin. In the present work, the role of glycosylation in the secretion of laminin and in the disulfide bonding of laminin subunits was studied, using tunicamycin to inhibit glycosylation. Tunicamycin inhibited extensively the secretion of laminin into culture medium and extracellular matrix even though the treated cells contained higher concentrations of laminin than the control cells. The laminin subunits synthesized in the presence of tunicamycin were disulfide bonded. Thus, suppression of glycosylation did not adversely affect disulfide bonding of the subunits, but did decrease the secretion of laminin. Glycosidases were also used to remove the carbohydrate of laminin to study the role of carbohydrate in the stability of laminin and in its interaction with another extracellular matrix component, heparin. The glycosidases removed about 73% of [3H]glucosamine. Both glycosidase-treated and untreated laminin were stable when incubated with cell lysate or culture medium. The glycosidase-treated laminin bound as efficiently as the untreated laminin to heparin. These results suggest that the presence of a carbohydrate moiety, at least at the level found in untreated laminin, is not essential in binding to heparin or in protecting laminin from proteolytic degradation in the cell or culture medium.


2015 ◽  
Vol 8 (2) ◽  
pp. 129-142 ◽  
Author(s):  
Barbara Pees ◽  
Wentao Yang ◽  
Alejandra Zárate-Potes ◽  
Hinrich Schulenburg ◽  
Katja Dierking

A key question in current immunity research is how the innate immune system can generate high levels of specificity. Evidence is accumulating that invertebrates, which exclusively rely on innate defense mechanisms, can differentiate between pathogens on the species and even strain level. In this review, we identify and discuss the particular potential of C-type lectin-like domain (CTLD) proteins to generate high immune specificity. Whilst several CTLD proteins are known to act as pattern recognition receptors in the vertebrate innate immune system, the exact role of CTLD proteins in invertebrate immunity is much less understood. We show that CTLD genes are highly abundant in most metazoan genomes and summarize the current state of knowledge on CTLD protein function in insect, crustacean and nematode immune systems. We then demonstrate extreme CTLD gene diversification in the genomes of Caenorhabditis nematodes and provide an update of data from CTLD gene function studies in C. elegans, which indicate that the diversity of CTLD genes could contribute to immune specificity. In spite of recent achievements, the exact functions of the diversified invertebrate CTLD genes are still largely unknown. Our review therefore specifically discusses promising research approaches to rectify this knowledge gap.


2020 ◽  
Author(s):  
Alex Agelidis ◽  
Benjamin A. Turturice ◽  
Rahul K. Suryawanshi ◽  
Tejabhiram Yadavalli ◽  
Dinesh Jaishankar ◽  
...  

AbstractThe drive to withstand environmental stresses and defend against invasion is a universal trait extant in all forms of life. While numerous canonical signaling cascades have been characterized in detail, it remains unclear how these pathways interface to generate coordinated responses to diverse stimuli. To dissect these connections, we follow heparanase (HPSE), a protein best known for its endoglycosidic activity at the extracellular matrix but recently recognized to drive various forms of late stage disease through unknown mechanisms. Using herpes simplex virus-1 (HSV-1) infection as a model cellular perturbation, we demonstrate that HPSE acts beyond its established enzymatic role to restrict multiple forms of cell-intrinsic defense and facilitate host cell reprogramming by the invading pathogen. We reveal that cells devoid of HPSE are innately resistant to infection and counteract viral takeover through multiple amplified defense mechanisms. With a unique grasp of the fundamental processes of transcriptional regulation and cell death, HPSE represents a potent cellular intersection with broad therapeutic potential.


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