scholarly journals Neutrophil-associated responses to Vibrio cholerae infection in a natural host model

2021 ◽  
Author(s):  
Dustin A Farr ◽  
Dhrubajyoti Nag ◽  
Walter J Chazin ◽  
Simone A. Harrison ◽  
Ryan Thummel ◽  
...  
Keyword(s):  
Transition Metals ◽  
Immune Responses ◽  
Vibrio Cholerae ◽  
Intestinal Microbiome ◽  
Early Immune Response ◽  
Nutritional Immunity ◽  
Infection Inhibition ◽  
The Relationship ◽  
Infectious Cycle

Vibrio cholerae, the cause of human cholera, is an aquatic bacterium found in association with a variety of animals in the environment, including many teleost fish species. V. cholerae infection induces a pro-inflammatory response followed by a non-inflammatory convalescent phase. Neutrophils are integral to this early immune response. However, the relationship between the neutrophil-associated protein calprotectin and V. cholerae has not been investigated, nor have the effects of limiting transition metals on V. cholerae growth. Zebrafish are useful as a natural V. cholerae model as the entire infectious cycle can be recapitulated in the presence of an intact intestinal microbiome and mature immune responses. Here, we demonstrate that zebrafish produce a significant neutrophil, IL-8, and calprotectin response following V. cholerae infection. Bacterial growth was completely inhibited by purified calprotectin protein or the chemical chelator TPEN, but growth was recovered by addition of transition metals zinc and manganese. Expression of downstream calprotectin targets also significantly increased in the zebrafish. These findings are the first to illuminate the role of calprotectin and nutritional immunity in combating V. cholerae infection. Inhibition of V. cholerae growth through metal limitation may provide new approaches in the development of anti-V. cholerae therapeutics. This study also establishes a major role for calprotectin in combating infectious diseases in zebrafish.

scholarly journals Antibiotics in early life and childhood pre-B-ALL. Reasons to analyze a possible new piece in the puzzle

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
T. M. Cardesa-Salzmann ◽  
A. Simon ◽  
N. Graf
Keyword(s):  
Immune Responses ◽  
Early Life ◽  
Lymphoblastic Leukemia ◽  
Antibiotic Use ◽  
Intestinal Microbiome ◽  
Microbial Composition ◽  
Hematopoietic Stem ◽  
Childhood All ◽  
Host Immune Responses

AbstractAcute lymphoblastic leukemia (ALL) is the most common pediatric cancer with precursor B-cell ALL (pB-ALL) accounting for ~ 85% of the cases. Childhood pB-ALL development is influenced by genetic susceptibility and host immune responses. The role of the intestinal microbiome in leukemogenesis is gaining increasing attention since Vicente-Dueñas’ seminal work demonstrated that the gut microbiome is distinct in mice genetically predisposed to ALL and that the alteration of this microbiome by antibiotics is able to trigger pB-ALL in Pax5 heterozygous mice in the absence of infectious stimuli. In this review we provide an overview on novel insights on the role of the microbiome in normal and preleukemic hematopoiesis, inflammation, the effect of dysbiosis on hematopoietic stem cells and the emerging importance of the innate immune responses in the conversion from preleukemic to leukemic state in childhood ALL. Since antibiotics, which represent one of the most widely used medical interventions, alter the gut microbial composition and can cause a state of dysbiosis, this raises exciting epidemiological questions regarding the implications for antibiotic use in early life, especially in infants with a a preleukemic “first hit”. Sheading light through a rigorous study on this piece of the puzzle may have broad implications for clinical practice.

scholarly journals The Role of Interferons in Driving Susceptibility to Asthma Following Bronchiolitis: Controversies and Research Gaps

2021 ◽  
Vol 12 ◽  
Author(s):  
Heidi Makrinioti ◽  
Andrew Bush ◽  
James Gern ◽  
Sebastian Lennox Johnston ◽  
Nikolaos Papadopoulos ◽  
...  
Keyword(s):  
Immune Responses ◽  
Acute Infection ◽  
Respiratory Viruses ◽  
Future Research ◽  
Innate Immune Responses ◽  
Asthmatic Children ◽  
Recurrent Wheeze ◽  
The Relationship

Bronchiolitis is the most common cause of hospitalization in infancy and is associated with a higher risk for the development of childhood asthma. However, not all children hospitalized with bronchiolitis will develop asthma. The mechanisms underlying asthma development following bronchiolitis hospitalization are complex. Immune responses to respiratory viruses may underlie both bronchiolitis severity and long-term sequela (such as asthma). Interferons (IFNs) are important components of innate immune responses to respiratory viruses and could influence both asthma development and asthma exacerbations. However, the nature of the relationship between interferon production and wheezing illnesses is controversial. For example, low peripheral blood IFN responses at birth have been linked with recurrent wheeze and asthma development. In contrast, there is evidence that severe illnesses (e.g., hospitalization for bronchiolitis) are associated with increased IFN responses during acute infection (bronchiolitis hospitalization) and a higher risk for subsequent asthma diagnosis. Furthermore, mechanistic studies suggest that bronchial epithelial cells from asthmatic children have impaired IFN responses to respiratory viruses, which may enable increased viral replication followed by exaggerated secondary IFN responses. This review aims to discuss controversies around the role of IFNs as drivers of susceptibility to asthma development following bronchiolitis hospitalization. Past evidence from both mechanistic and cohort studies are discussed. We will highlight knowledge gaps that can inform future research study design.

scholarly journals Geometrical reorganization of Dectin-1 and TLR2 on single phagosomes alters their synergistic immune signaling

2019 ◽  
Vol 116 (50) ◽  
pp. 25106-25114 ◽  
Author(s):  
Wenqian Li ◽  
Jun Yan ◽  
Yan Yu
Keyword(s):  
Immune Responses ◽  
Immune Regulation ◽  
Spatial Organization ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Membrane Composition ◽  
Intracellular Compartments ◽  
Synergistic Regulation ◽  
The Relationship

Receptors of innate immune cells function synergistically to detect pathogens and elicit appropriate immune responses. Many receptor pairs also appear “colocalized” on the membranes of phagosomes, the intracellular compartments for pathogen ingestion. However, the nature of the seemingly receptor colocalization and the role it plays in immune regulation are unclear, due to the inaccessibility of intracellular phagocytic receptors. Here, we report a geometric manipulation technique to directly probe the role of phagocytic receptor “colocalization” in innate immune regulation. Using particles with spatially patterned ligands as phagocytic targets, we can decouple the receptor pair, Dectin-1 and Toll-like receptor (TLR)2, to opposite sides on a single phagosome or bring them into nanoscale proximity without changing the overall membrane composition. We show that Dectin-1 enhances immune responses triggered predominantly by TLR2 when their centroid-to-centroid proximity is <500 nm, but this signaling synergy diminishes upon receptor segregation beyond this threshold distance. Our results demonstrate that nanoscale proximity, not necessarily colocalization, between Dectin-1 and TLR2 is required for their synergistic regulation of macrophage immune responses. This study elucidates the relationship between the spatial organization of phagocytic receptors and innate immune responses. It showcases a technique that allows spatial manipulation of receptors and their signal cross-talk on phagosomes inside living cells.

The rôle of cortisol and β-endorphin in the response of the immune system to weaning in lambs

1998 ◽  
Vol 66 (2) ◽  
pp. 397-402 ◽  
Author(s):  
S. M. Rhind ◽  
H. W. Reid ◽  
S. R. McMillen ◽  
G. Palmarini
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Stress Hormone ◽  
Keyhole Limpet Haemocyanin ◽  
Weaning Stress ◽  
Cell Mediated Immune Response ◽  
Acth Treatment ◽  
Induced Changes ◽  
The Relationship

AbstractThe relationship between weaning stress-induced changes in stress hormone profiles and immune function was investigated in groups of 10 lambs immunized against adrenocorticotrophic hormone (ACTH; treatment A) or fi-endorphin (treatment B) to reduce the circulating concentrations of cortisol and fi-endorphin respectively. Control animals (treatment C) were immunized against a porcine thyroglobulin carrier protein. Application of weaning stress was associated with significantly elevated plasma cortisol concentrations but no significant increase in fi-endorphin concentrations in C lambs. Immunization against ACTH suppressed the post-weaning increase in cortisol concentration. This was associated with a transient reduction in the lymphocyte stimulation response to keyhole limpet haemocyanin (KLH) antigen in the A animals but there was no effect on the antibody response or interferon-y production by antigen stimulated lymphocytes. There were no significant effects of immunization against fi-endorphin on the capacity to mount antibody or cell-mediated immune responses. It is concluded that weaning stress-induced increases in cortisol did not inhibit the immune response. Since cortisol concentrations and the cell mediated immune response at 8 days after immunization were positively associated it is concluded that these indices are not independent measures of stress.

scholarly journals Vibrio cholerae at the Intersection of Immunity and the Microbiome

mSphere ◽  
2019 ◽  
Vol 4 (6) ◽  
Author(s):  
Ana A. Weil ◽  
Rachel L. Becker ◽  
Jason B. Harris
Keyword(s):  
Immune Response ◽  
Small Intestine ◽  
Immune Responses ◽  
Cholera Toxin ◽  
Vibrio Cholerae ◽  
Intestinal Microbiome ◽  
Secretory Diarrhea ◽  
Content Type ◽  
New Approaches

ABSTRACT Vibrio cholerae is a noninvasive pathogen that colonizes the small intestine and produces cholera toxin, causing severe secretory diarrhea. Cholera results in long lasting immunity, and recent studies have improved our understanding of the antigenic repertoire of V. cholerae. Interactions between the host, V. cholerae, and the intestinal microbiome are now recognized as factors which impact susceptibility to cholera and the ability to mount a successful immune response to vaccination. Here, we review recent data and corresponding models to describe immune responses to V. cholerae infection and explain how the host microbiome may impact the pathogenesis of V. cholerae. In the ongoing battle against cholera, the intestinal microbiome represents a frontier for new approaches to intervention and prevention.

scholarly journals Diverticular Disease: a Gut Microbiota Perspective

2019 ◽  
Vol 28 (3) ◽  
pp. 327-337 ◽  
Author(s):  
Andrea Ticinesi ◽  
Antonio Nouvenne ◽  
Vincenzo Corrente ◽  
Claudio Tana ◽  
Francesco Di Mario ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Diverticular Disease ◽  
Intestinal Microbiome ◽  
Microbiota Composition ◽  
Future Studies ◽  
Abdominal Symptoms ◽  
Uncertain Future ◽  
The Relationship ◽  
Gut Microbiota Composition

Gut microbiota composition and functionality are involved in the pathophysiology of several intestinal andextraintestinal diseases, and are increasingly considered a modulator of local and systemic inflammation.However, the involvement of gut microbiota in diverticulosis and in diverticular disease is still poorlyinvestigated. In this review, we critically analyze the existing evidence on the fecal and mucosa-associatedmicrobiota composition and functionality across different stages of diverticular disease. We also explorethe influence of risk factors for diverticulosis on gut microbiota composition, and speculate on the possiblerelevance of these associations for the pathogenesis of diverticula. We overview the current treatments ofdiverticular disease targeting the intestinal microbiome, highlighting the current areas of uncertainty andthe need for future studies. Although no conclusive remarks on the relationship between microbiota anddiverticular disease can be made, preliminary data suggest that abdominal symptoms are associated withreduced representation of taxa with a possible anti-inflammatory effect, such as Clostridium cluster IV, andovergrowth of Enterobacteriaceae, Bifidobacteria and Akkermansia. The role of the microbiota in the earlystages of the disease is still very uncertain. Future studies should help to disentangle the role of the microbiomein the pathogenesis of diverticular disease and its progression towards more severe forms.

scholarly journals The Mammalian Intestinal Microbiome: Composition, Interaction with the Immune System, Significance for Vaccine Efficacy, and Potential for Disease Therapy

Pathogens ◽  
2018 ◽  
Vol 7 (3) ◽  
pp. 57 ◽  
Author(s):  
Ulrich Desselberger
Keyword(s):  
Immune Responses ◽  
Gut Microbiome ◽  
Molecular Mechanisms ◽  
Gut Bacteria ◽  
Intestinal Microbiome ◽  
Fecal Microbiome ◽  
Microbiome Composition ◽  
Disease Therapy ◽  
Intestinal Pathogens ◽  
The Relationship

The mammalian gut is colonized by a large variety of microbes, collectively termed ‘the microbiome’. The gut microbiome undergoes rapid changes during the first few years of life and is highly variable in adulthood depending on various factors. With the gut being the largest organ of immune responses, the composition of the microbiome of the gut has been found to be correlated with qualitative and quantitative differences of mucosal and systemic immune responses. Animal models have been very useful to unravel the relationship between gut microbiome and immune responses and for the understanding of variations of immune responses to vaccination in different childhood populations. However, the molecular mechanisms underlying optimal immune responses to infection or vaccination are not fully understood. The gut virome and gut bacteria can interact, with bacteria facilitating viral infectivity by different mechanisms. Some gut bacteria, which have a beneficial effect on increasing immune responses or by overgrowing intestinal pathogens, are considered to act as probiotics and can be used for therapeutic purposes (as in the case of fecal microbiome transplantation).

scholarly journals Impact of Zinc, Glutathione, and Polyphenols as Antioxidants in the Immune Response against SARS-CoV-2

Processes ◽  
2021 ◽  
Vol 9 (3) ◽  
pp. 506
Author(s):  
José Manuel Pérez de la Lastra ◽  
Celia Andrés-Juan ◽  
Francisco J. Plou ◽  
Eduardo Pérez-Lebeña
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Immune Responses ◽  
Rational Design ◽  
Global Scale ◽  
Key Factors ◽  
Central Function ◽  
Antiviral Immune Response ◽  
The Relationship

SARS-CoV-2, the coronavirus triggering the disease COVID-19, has a catastrophic health and socioeconomic impact at a global scale. Three key factors contribute to the pathogenesis of COVID-19: excessive inflammation, immune system depression/inhibition, and a set of proinflammatory cytokines. Common to these factors, a central function of oxidative stress has been highlighted. A diversity of clinical trials focused predominantly on antioxidants are being implemented as potential therapies for COVID-19. In this study, we look at the role of zinc, glutathione, and polyphenols, as key antioxidants of possible medicinal or nutritional significance, and examine their role in the antiviral immune response induced by SARS-Cov-2. An unresolved question is why some people experience chronic COVID and others do not. Understanding the relationship between SARS-CoV-2 and the immune system, as well as the role of defective immune responses to disease development, would be essential to recognize the pathogenesis of COVID-19, the risk factors that affect the harmful consequences of the disease, and the rational design of successful therapies and vaccinations. We expect that our research will provide a novel perspective that contributes to the design of clinical or nutritional targets for the prevention of this pandemic.

scholarly journals Saving Death: Apoptosis for Intervention in Transplantation and Autoimmunity

2006 ◽  
Vol 13 (2-4) ◽  
pp. 273-282 ◽  
Author(s):  
Alice Li ◽  
Okechukwu Ojogho ◽  
Alan Escher
Keyword(s):  
Immune Responses ◽  
Transplant Rejection ◽  
Apoptotic Cells ◽  
Regulatory Cells ◽  
Immune Mediated ◽  
Immunological Homeostasis ◽  
The Relationship ◽  
Induction Of Tolerance ◽  
Naive T Lymphocytes

Long considered immunologically “bland,” apoptotic cells are now recognized as important modulators of immune responses. The role of apoptosis in immunological homeostasis has been inferred from several findings, for example, induction of tolerance after injection of apoptotic cells and the capacity of APCs like macrophages and DCs to induce and maintain tolerance after phagocytosis of dead cells. Processing of apoptotic cells by DCs is of particular interest, because DCs are the only known APCs capable of activating naïve T lymphocytes to become effector or regulatory cells. In that regard, recent evidence suggests that phagocytosis of apoptotic cells by DCs can induce Tregs, a finding that has significant implications for the treatment of a variety of immune-mediated inflammatory disorders. Here, we review the relationship between apoptotic cells, DCs, and Tregs, and its impact on prevention of transplant rejection and treatment of autoimmune diseases.

Choosing a Markov blanket

2020 ◽  
Vol 43 ◽  
Author(s):  
Thomas Parr
Keyword(s):  
Markov Blanket ◽  
Target Article ◽  
The Relationship

Abstract This commentary focuses upon the relationship between two themes in the target article: the ways in which a Markov blanket may be defined and the role of precision and salience in mediating the interactions between what is internal and external to a system. These each rest upon the different perspectives we might take while “choosing” a Markov blanket.

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