3 MECHANSISMS OF INTESTINAL FUNGI RECOGNITION AND CONTROL

2020 ◽  
Vol 26 (Supplement_1) ◽  
pp. S41-S41
Author(s):  
Irina Leonardi ◽  
Iliyan Iliev
Keyword(s):  
Steady State ◽  
Immune Responses ◽  
Antigen Presentation ◽  
Intestinal Inflammation ◽  
Mononuclear Phagocytes ◽  
Fungal Communities ◽  
Cellular Mechanisms ◽  
Anti Fungal ◽  
And Control

Abstract Background and Objectives Intestinal fungal communities are perturbed in several autoimmune diseases and have been shown to influence disease outcome. We have shown that intestinal resident CX3CR1+ mononuclear phagocytes (MNPs) can sense gut fungi and are crucial for the initiation of immune responses both locally and at distant sites. These results suggest that recognition of fungi by gut phagocytes might be involved in the pathogenesis of immune-related diseases such as IBD. Despite the identification of a few molecules involved in the recognition and immunity to intestinal fungi the cellular mechanisms governing the initiation and regulation of the mucosal immune responses to the mycobiota remain unknown. We sought to identify the functional role of distinct phagocytic subsets in the response to fungal communities in the gut during health and intestinal disease. Methods We used Candida albicans, the main opportunistic fungus found in IBD patients, as model fungal colonizer, with a focus on the mechanisms mediating the adaptive response. To elucidate the mechanisms and consequences of the recognition of fungi by phagocytic subsets in the lamina propria we used genetic models of depletion and deletion of specific subtypes of phagocytes. We further targeted fungal recognition and antigen presentation in phagocytes to investigate the mechanisms leading to the induction of adaptive anti-fungal responses. Results C. albicans colonization induced a consistent increase in Th17 cells in the intestinal mucosa that was decreased upon depletion of CX3CR1+ MNPs. Genetic depletion of CX3CR1+ MNPs in mice led to changes in gut fungal communities and to severe chemically induced intestinal inflammation that was rescued by antifungal treatment. Recognition of fungi through a C-type lectin/Syk pathways and antigen presentation via MHC-II were necessary for the induction of adaptive T cell in responses to C. albicans colonization. Conclusion Our work aims at defining the role of CX3CR1+ MNPs and cDCs in the initiation of anti-fungal immune responses in the intestine at the steady state. We have demonstrated the essential role of CX3CR1+ MNPs in the initiation of antifungal responses in the intestine at steady state and for the control of fungi at steady state and during inflammation. We have demonstrated the importance of CX3CR1+ MNPs in the control of the intestinal mycobiota.

scholarly journals CX3CR1+mononuclear phagocytes control immunity to intestinal fungi

Science ◽  
2018 ◽  
Vol 359 (6372) ◽  
pp. 232-236 ◽  
Author(s):  
Irina Leonardi ◽  
Xin Li ◽  
Alexa Semon ◽  
Dalin Li ◽  
Itai Doron ◽  
...  
Keyword(s):  
Immune Responses ◽  
Inflammatory Disease ◽  
Mononuclear Phagocytes ◽  
Fungal Communities ◽  
Dependent Manner ◽  
Gene Encoding ◽  
Genetic Ablation ◽  
Adaptive Immune ◽  
Severe Colitis

Intestinal fungi are an important component of the microbiota, and recent studies have unveiled their potential in modulating host immune homeostasis and inflammatory disease. Nonetheless, the mechanisms governing immunity to gut fungal communities (mycobiota) remain unknown. We identified CX3CR1+mononuclear phagocytes (MNPs) as being essential for the initiation of innate and adaptive immune responses to intestinal fungi. CX3CR1+MNPs express antifungal receptors and activate antifungal responses in a Syk-dependent manner. Genetic ablation of CX3CR1+MNPs in mice led to changes in gut fungal communities and to severe colitis that was rescued by antifungal treatment. In Crohn’s disease patients, a missense mutation in the gene encoding CX3CR1 was identified and found to be associated with impaired antifungal responses. These results unravel a role of CX3CR1+MNPs in mediating interactions between intestinal mycobiota and host immunity at steady state and during inflammatory disease.

Physiological effects of endogenous ouabain: control of intracellular Ca2+ stores and cell responsiveness

1993 ◽  
Vol 264 (6) ◽  
pp. C1367-C1387 ◽  
Author(s):  
M. P. Blaustein
Keyword(s):  
Steady State ◽  
Cell Types ◽  
Whole Body ◽  
Cellular Mechanisms ◽  
Signaling Mechanism ◽  
Physiological Processes ◽  
Endogenous Ouabain ◽  
Adrenal Cortical Hormone ◽  
Salt And Water Balance

Ouabain is a well-known compound but a newly discovered adrenal cortical hormone that plays a role in cell Na+ regulation and in whole body salt and water balance. Ouabain may also be a paracrine hormone and may be secreted by some central nervous system neurons as well as by other types of cells. This article focuses on the cellular mechanisms that underlie the physiological (and pathophysiological) effects of ouabain. Ouabain directly inhibits the plasmalemmal Na+ pump in a variety of cell types. Low ouabain concentrations cause, in the steady state, a modest rise in the cytosolic Na+ concentration but only a minimal decline in membrane potential. All Na+ gradient-dependent processes may thereby be affected, albeit to only a small extent. Most important, however, is the secondary redistribution of Ca2+, mediated by Na(+)-Ca2+ exchange, that should slightly increase the cytosolic free Ca2+ concentration ([Ca2+]cyt). As a result of Ca2+ sequestration in intracellular stores [the endoplasmic and/or sarcoplasmic reticulum (ER/SR)], however, a new steady state is achieved with a slightly increased [Ca2+]cyt but a substantially augmented Ca2+ store; thus the ER/SR effectively acts as a Ca2+ amplifier. This extra stored Ca2+ is then available for mobilization whenever the cells are activated. Cytosolic Ca2+ is a key signaling mechanism in virtually all cells: it controls numerous physiological processes such as contraction, secretion, and excitability. Thus ouabain may modulate cell responsiveness via its influence on ER/SR Ca2+ stores. With these principles in mind, we examine evidence that endogenous ouabain may play a role in numerous physiological and pathophysiological processes associated with altered fluid and electrolyte metabolism and deviations from the normal blood pressure-blood volume relationship. We discuss the possible participation of ouabain in the regulation of vascular tone and then consider the putative role of ouabain in several forms of hypertension, congestive heart failure, thyroid and adrenocortical dysfunction, and diabetes mellitus, as well as in the adaptation to high altitude.

scholarly journals Phagocytosis: A Fundamental Process in Immunity

2017 ◽  
Vol 2017 ◽  
pp. 1-18 ◽  
Author(s):  
Carlos Rosales ◽  
Eileen Uribe-Querol
Keyword(s):  
Immune Responses ◽  
Host Response ◽  
Current Knowledge ◽  
General View ◽  
Cellular Mechanisms ◽  
Complex Process ◽  
Fundamental Process ◽  
Target Particle ◽  
Acquired Immune Responses

One hundred years have passed since the death of Élie Metchnikoff (1845–1916). He was the first to observe the uptake of particles by cells and realized the importance of this process for the host response to injury and infection. He also was a strong advocate of the role of phagocytosis in cellular immunity, and with this he gave us the basis for our modern understanding of inflammation and the innate and acquired immune responses. Phagocytosis is an elegant but complex process for the ingestion and elimination of pathogens, but it is also important for the elimination of apoptotic cells and hence fundamental for tissue homeostasis. Phagocytosis can be divided into four main steps: (i) recognition of the target particle, (ii) signaling to activate the internalization machinery, (iii) phagosome formation, and (iv) phagolysosome maturation. In recent years, the use of new tools of molecular biology and microscopy has provided new insights into the cellular mechanisms of phagocytosis. In this review, we present a general view of our current knowledge on phagocytosis. We emphasize novel molecular findings, particularly on phagosome formation and maturation, and discuss aspects that remain incompletely understood.

scholarly journals Wheat amylase trypsin inhibitors drive intestinal inflammation via activation of toll-like receptor 4

2012 ◽  
Vol 209 (13) ◽  
pp. 2395-2408 ◽  
Author(s):  
Yvonne Junker ◽  
Sebastian Zeissig ◽  
Seong-Jun Kim ◽  
Donatella Barisani ◽  
Herbert Wieser ◽  
...  
Keyword(s):  
Celiac Disease ◽  
Immune Responses ◽  
Intestinal Inflammation ◽  
Storage Proteins ◽  
Trypsin Inhibitors ◽  
Innate Immune Responses ◽  
Toll Like Receptor 4 ◽  
Wheat Amylase ◽  
Hla Dq2

Ingestion of wheat, barley, or rye triggers small intestinal inflammation in patients with celiac disease. Specifically, the storage proteins of these cereals (gluten) elicit an adaptive Th1-mediated immune response in individuals carrying HLA-DQ2 or HLA-DQ8 as major genetic predisposition. This well-defined role of adaptive immunity contrasts with an ill-defined component of innate immunity in celiac disease. We identify the α-amylase/trypsin inhibitors (ATIs) CM3 and 0.19, pest resistance molecules in wheat, as strong activators of innate immune responses in monocytes, macrophages, and dendritic cells. ATIs engage the TLR4–MD2–CD14 complex and lead to up-regulation of maturation markers and elicit release of proinflammatory cytokines in cells from celiac and nonceliac patients and in celiac patients’ biopsies. Mice deficient in TLR4 or TLR4 signaling are protected from intestinal and systemic immune responses upon oral challenge with ATIs. These findings define cereal ATIs as novel contributors to celiac disease. Moreover, ATIs may fuel inflammation and immune reactions in other intestinal and nonintestinal immune disorders.

scholarly journals Murine CXCL14 Is Dispensable for Dendritic Cell Function and Localization within Peripheral Tissues

2006 ◽  
Vol 27 (3) ◽  
pp. 983-992 ◽  
Author(s):  
Simone Meuter ◽  
Patrick Schaerli ◽  
Regula Stuber Roos ◽  
Oliver Brandau ◽  
Michael R. Bösl ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cell Function ◽  
Physiological Function ◽  
Dendritic Cell Function ◽  
Peripheral Tissues ◽  
Significant Difference ◽  
Antigen Presenting ◽  
And Control

ABSTRACT Dendritic cells (DCs) have long been recognized as key regulators of immune responses. However, the process of their recruitment to peripheral tissues and turnover during homeostasis remains largely unknown. The chemokine CXCL14 (BRAK) is constitutively expressed in skin and other epithelial tissues. Recently, the human chemokine was proposed to play a role in the homeostatic recruitment of macrophage and/or DC precursors toward the periphery, such as skin. Although so far no physiological function could be demonstrated for the murine CXCL14, it shows a remarkable homology to the human chemokine. In order to elucidate the in vivo role of CXCL14, we generated a mouse defective for this chemokine. We studied various components of the immune system with emphasis on monocytes/macrophages and DC/Langerhans cell (LC) populations in different tissues during steady state but did not find a significant difference between knockout (CXCL14 − / −) and control mice. Functionally, LCs were able to become activated, to migrate out of skin, and to elicit a delayed type of hypersensitivity reaction. Overall, our data indicate that murine CXCL14 is dispensable for the homeostatic recruitment of antigen-presenting cells toward the periphery and for LC functionality.

scholarly journals Bacillus amyloliquefaciens TL Downregulates the Ileal Expression of Genes Involved in Immune Responses in Broiler Chickens to Improve Growth Performance

2021 ◽  
Vol 9 (2) ◽  
pp. 382
Author(s):  
Yuxuan Hong ◽  
Yang Cheng ◽  
Leluo Guan ◽  
Zutao Zhou ◽  
Xiaowen Li ◽  
...  
Keyword(s):  
Immune Responses ◽  
Bacillus Amyloliquefaciens ◽  
Broiler Chickens ◽  
Intestinal Inflammation ◽  
Functional Enrichment ◽  
Receptor Interaction ◽  
Control Group ◽  
Intestinal Damage ◽  
Expression Of Genes ◽  
And Control

Bacillus amyloliquefaciens TL promotes broiler chicken performance by improving nutrient absorption and utilization and reducing intestinal inflammation. In this study, RNA-sequencing (RNA-seq)-based transcriptomes of ileal tissues collected from probiotic-fed and control broiler chickens were analyzed to elucidate the effects of the probiotic B. amyloliquefaciens TL, as a feed additive, on the gut immune function. In total, 475 genes were significantly differentially expressed between the ileum of probiotic-fed and control birds. The expression of genes encoding pyruvate kinase, prothymosin-α, and heat stress proteins was high in the ileum of probiotic-fed birds (FPKM > 500), but not in the control group. The gene ontology functional enrichment and pathway enrichment analyses revealed that the uniquely expressed genes in the control group were mostly involved in immune responses, whereas those in the probiotic group were involved in fibroblast growth factor receptor signaling pathways and positive regulation of cell proliferation. Bacillus amyloliquefaciens TL downregulated the expression of certain proinflammatory factors and affected the cytokine–cytokine receptor interaction pathway. Furthermore, B. amyloliquefaciens TL in broiler diets altered the expression of genes involved in immune functions in the ileum. Thus, it might contribute to improved broiler growth by regulating the immune system and reducing intestinal damage in broilers.

Evaluation of role of G-CSF in the production, survival, and release of neutrophils from bone marrow into circulation

Blood ◽  
2002 ◽  
Vol 100 (3) ◽  
pp. 854-861 ◽  
Author(s):  
Sunanda Basu ◽  
George Hodgson ◽  
Melissa Katz ◽  
Ashley R. Dunn
Keyword(s):  
Bone Marrow ◽  
Steady State ◽  
Transit Time ◽  
Bone Marrow Cells ◽  
Mean Transit Time ◽  
Wild Type ◽  
Blast Cells ◽  
And Control ◽  
Deficient Mice

Abstract In steady-state hematopoiesis, G-CSF (granulocyte-colony stimulating factor) regulates the level of neutrophils in the bone marrow and blood. In this study, we have exploited the availability of G-CSF–deficient mice to evaluate the role of G-CSF in steady-state granulopoiesis and the release of granulocytes from marrow into circulation. The thymidine analogue bromodeoxyuridine (BrdU) was used to label dividing bone marrow cells, allowing us to follow the release of granulocytes into circulation. Interestingly, the labeling index and the amount of BrdU incorporated by blast cells in bone marrow was greater in G-CSF–deficient mice than in wild-type mice. In blood, 2 different populations of BrdU-positive granulocytes, BrdUbright and BrdUdim, could be detected. The kinetics of release of the BrdUbright granulocytes from bone marrow into blood was similar in wild-type and G-CSF–deficient mice; however, BrdUdim granulocytes peaked earlier in G-CSF–deficient mice. Our findings suggest that the mean transit time of granulocytes through the postmitotic pool is similar in G-CSF–deficient and control mice, although the transit time through the mitotic pool is reduced in G-CSF–deficient mice. Moreover, the reduced numbers of granulocytes that characterize G-CSF–deficient mice is primarily due to increased apoptosis in cells within the granulocytic lineage. Collectively, our data suggest that at steady state, G-CSF is critical for the survival of granulocytic cells; however, it is dispensable for trafficking of granulocytes from bone marrow into circulation.

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