Evaluation of in vivo and in vitro effectivity of immune defense against a spontaneously arising, nonlymphoid rat tumor

1985 ◽  
Vol 19 (3) ◽  
pp. 183-188 ◽  
Author(s):  
Margot Zöller
Keyword(s):  
Immune Defense ◽  
Rat Tumor

scholarly journals Combined Stimulation of Toll-Like Receptor 5 and NOD1 Strongly Potentiates Activity of NF-κB, Resulting in Enhanced Innate Immune Reactions and Resistance to Salmonella enterica Serovar Typhimurium Infection

2013 ◽  
Vol 81 (10) ◽  
pp. 3855-3864 ◽  
Author(s):  
Amir I. Tukhvatulin ◽  
Ilya I. Gitlin ◽  
Dmitry V. Shcheblyakov ◽  
Natalia M. Artemicheva ◽  
Lyudmila G. Burdelya ◽  
...  
Keyword(s):  
Critical Role ◽  
Immune Defense ◽  
Innate Immune ◽  
Microbial Infection ◽  
Immune Reactions ◽  
Content Type ◽  
Essential Components ◽  
Stimulation Of

ABSTRACTPathogen recognition receptors (PRRs) are essential components of host innate immune systems that detect specific conserved pathogen-associated molecular patterns (PAMPs) presented by microorganisms. Members of two families of PRRs, transmembrane Toll-like receptors (TLRs 1, 2, 4, 5, and 6) and cytosolic NOD receptors (NOD1 and NOD2), are stimulated upon recognition of various bacterial PAMPs. Such stimulation leads to induction of a number of immune defense reactions, mainly triggered via activation of the transcription factor NF-κB. While coordination of responses initiated via different PRRs sensing multiple PAMPS present during an infection makes clear biological sense for the host, such interactions have not been fully characterized. Here, we demonstrate that combined stimulation of NOD1 and TLR5 (as well as other NOD and TLR family members) strongly potentiates activity of NF-κB and induces enhanced levels of innate immune reactions (e.g., cytokine production) bothin vitroandin vivo. Moreover, we show that an increased level of NF-κB activity plays a critical role in formation of downstream responses. In live mice, synergy between these receptors resulting in potentiation of NF-κB activity was organ specific, being most prominent in the gastrointestinal tract. Coordinated activity of NOD1 and TLR5 significantly increased protection of mice against enteroinvasiveSalmonellainfection. Obtained results suggest that cooperation of NOD and TLR receptors is important for effective responses to microbial infectionin vivo.

scholarly journals Cell-specific qRT-PCR of renal epithelial cells reveals a novel innate immune signature in murine collecting duct

2018 ◽  
Vol 315 (4) ◽  
pp. F812-F823 ◽  
Author(s):  
Vijay Saxena ◽  
David S. Hains ◽  
John Ketz ◽  
Melinda Chanley ◽  
John D. Spencer ◽  
...  
Keyword(s):  
Urinary Tract ◽  
Mrna Expression ◽  
Collecting Duct ◽  
Immune Defense ◽  
Innate Immune ◽  
Targeted Analysis ◽  
Collecting Tubule ◽  
Tubule Cells

The urinary tract is usually culture negative despite its close proximity to microbial flora. The precise mechanism by which the kidneys and urinary tract defends against infection is not well understood. The initial kidney cells to encounter ascending pathogens are the collecting tubule cells that consist of principal cells (PCs) that express aquaporin 2 (AQP2) and intercalated cells (ICs) that express vacuolar H+-ATPase (V-ATPase, B1 subunit). We have previously shown that ICs are involved with the human renal innate immune defense. Here we generated two reporter mice, VATPase B1-cre+tdT+mice to fluorescently label ICs and AQP2-cre+tdT+mice to fluorescently label PCs, and then performed flow sorting to enrich PCs and ICs for analysis. Isolated ICs and PCs along with proximal tubular cells were used to measure antimicrobial peptide (AMP) mRNA expression. ICs and PCs were significantly enriched for AMPs. Isolated ICs responded to uropathogenic Escherichia coli (UPEC) challenge in vitro and had higher RNase4 gene expression than control while both ICs and PCs responded to UPEC challenge in vivo by upregulating Defb1 mRNA expression. To our knowledge, this is the first report of isolating murine collecting tubule cells and performing targeted analysis for multiple classes of AMPs.

scholarly journals Differential Regulation of β-Defensin Gene Expression during Cryptosporidium parvum Infection

2004 ◽  
Vol 72 (5) ◽  
pp. 2772-2779 ◽  
Author(s):  
Tarek K. Zaalouk ◽  
Mona Bajaj-Elliott ◽  
John T. George ◽  
Vincent McDonald
Keyword(s):  
Gene Expression ◽  
Cryptosporidium Parvum ◽  
Protozoan Parasite ◽  
Immune Defense ◽  
Microbial Pathogens ◽  
In Vivo Models ◽  
Defensin Gene ◽  
Intestinal Epithelia

ABSTRACT Invasion of enterocytes by pathogenic microbes evokes both innate and adaptive immune responses, and microbial pathogens have developed strategies to overcome the initial host immune defense. β-Defensins are potentially important endogenous antibiotic-like effectors of innate immunity expressed by intestinal epithelia. In this study, the interplay between the enteric protozoan parasite Cryptosporidium parvum and host epithelial β-defensin expression was investigated. Using human and murine models of infection, we demonstrated that C. parvum infection differentially regulates β-defensin gene expression. Downregulation of murine β-defensin-1 mRNA and protein was observed in both in vitro and in vivo models of infection. Infection of the human colonic HT29 cell line with the parasite resulted in differential effects on various members of the defensin gene family. Partial reduction in human β-defensin-1 (hBD-1), induction of hBD-2, and no effect on hBD-3 gene expression was observed. Recombinant hBD-1 and hBD-2 peptides exhibited significant antimicrobial activity against C. parvum sporozoites in vitro. These findings demonstrate that C. parvum infection of enterocytes may affect the expression of various defensins in different ways and suggest that the overall outcome of the effect of antimicrobial peptides on early survival of the parasite may be complex.

scholarly journals How Neutrophil Extracellular Traps Become Visible

2016 ◽  
Vol 2016 ◽  
pp. 1-13 ◽  
Author(s):  
Nicole de Buhr ◽  
Maren von Köckritz-Blickwede
Keyword(s):  
Electron Microscopy ◽  
Nuclear Dna ◽  
Defense Mechanism ◽  
Neutrophil Extracellular Traps ◽  
Immune Defense ◽  
Extracellular Traps ◽  
Activated Neutrophils ◽  
Microscopy Techniques

Neutrophil extracellular traps (NETs) have been identified as a fundamental innate immune defense mechanism against different pathogens. NETs are characterized as released nuclear DNA associated with histones and granule proteins, which form an extracellular web-like structure that is able to entrap and occasionally kill certain microbes. Furthermore, NETs have been shown to contribute to several noninfectious disease conditions when released by activated neutrophils during inflammation. The identification of NETs has mainly been succeeded by various microscopy techniques, for example, immunofluorescence microscopy, transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Since the last years the development and improvement of new immunofluorescence-based techniques enabled optimized visualization and quantification of NETs. On the one handin vitrolive-cell imaging led to profound new ideas about the mechanisms involved in the formation and functionality of NETs. On the other hand different intravital,in vivo, andin situmicroscopy techniques led to deeper insights into the role of NET formation during health and disease. This paper presents an overview of the main used microscopy techniques to visualize NETs and describes their advantages as well as disadvantages.

scholarly journals Surfactant Protein D Increases Phagocytosis of Hypocapsular Cryptococcus neoformans by Murine Macrophages and Enhances Fungal Survival

2009 ◽  
Vol 77 (7) ◽  
pp. 2783-2794 ◽  
Author(s):  
Scarlett Geunes-Boyer ◽  
Timothy N. Oliver ◽  
Guilhem Janbon ◽  
Jennifer K. Lodge ◽  
Joseph Heitman ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Defense Mechanisms ◽  
Protein A ◽  
Surfactant Protein ◽  
Immune Defense ◽  
Surfactant Protein D ◽  
Wild Type ◽  
Phagocytic Cells

ABSTRACT Cryptococcus neoformans is a facultative intracellular opportunistic pathogen and the leading cause of fungal meningitis in humans. In the absence of a protective cellular immune response, the inhalation of C. neoformans cells or spores results in pulmonary infection. C. neoformans cells produce a polysaccharide capsule composed predominantly of glucuronoxylomannan, which constitutes approximately 90% of the capsular material. In the lungs, surfactant protein A (SP-A) and SP-D contribute to immune defense by facilitating the aggregation, uptake, and killing of many microorganisms by phagocytic cells. We hypothesized that SP-D plays a role in C. neoformans pathogenesis by binding to and enhancing the phagocytosis of the yeast. Here, the abilities of SP-D to bind to and facilitate the phagocytosis and survival of the wild-type encapsulated strain H99 and the cap59Δ mutant hypocapsular strain are assessed. SP-D binding to cap59Δ mutant cells was approximately sixfold greater than binding to wild-type cells. SP-D enhanced the phagocytosis of cap59Δ cells by approximately fourfold in vitro. To investigate SP-D binding in vivo, SP-D−/− mice were intranasally inoculated with Alexa Fluor 488-labeled cap59Δ or H99 cells. By confocal microscopy, a greater number of phagocytosed C. neoformans cells in wild-type mice than in SP-D−/− mice was observed, consistent with in vitro data. Interestingly, SP-D protected C. neoformans cells against macrophage-mediated defense mechanisms in vitro, as demonstrated by an analysis of fungal viability using a CFU assay. These findings provide evidence that C. neoformans subverts host defense mechanisms involving surfactant, establishing a novel virulence paradigm that may be targeted for therapy.

scholarly journals TLR-induced reorganization of the IgM-BCR complex regulates B-1 cell responses to infections

2019 ◽  
Author(s):  
Hannah P. Savage ◽  
Kathrin Kläsener ◽  
Fauna L. Smith ◽  
Zheng Luo ◽  
Michael Reth ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Salmonella Typhimurium ◽  
Immune Defense ◽  
Concomitant Increase ◽  
Downstream Signaling ◽  
Cell Responses ◽  
Bcr Signaling ◽  
Eventual Loss

AbstractNeonatally-developing, self-reactive B-1 cells generate steady levels natural antibodies throughout life. They can, however, also rapidly respond to infections with increased local antibody production. The mechanisms regulating these two seemingly very distinct functions are poorly understood, but have been linked to expression of CD5, an inhibitor of BCR-signaling. Here we demonstrate that TLR-mediated activation of CD5+ B-1 cells induced the rapid reorganization of the IgM-BCR complex, leading to the eventual loss of CD5 expression, and a concomitant increase in BCR-downstream signaling, both in vitro and in vivo after infections with influenza virus and Salmonella typhimurium. Both, initial CD5 expression and TLR-mediated stimulation, were required for the differentiation of B-1 cells to IgM-producing plasmablasts after infections. Thus, TLR-mediated signals support participation of B-1 cells in immune defense via BCR-complex reorganization.

Alcohol-induced downregulation of superoxide anion release by hepatic phagocytes in endotoxemic rats

1991 ◽  
Vol 260 (5) ◽  
pp. R969-R976
Author(s):  
A. P. Bautista ◽  
N. B. D'Souza ◽  
C. H. Lang ◽  
J. Bagwell ◽  
J. J. Spitzer
Keyword(s):  
Kupffer Cells ◽  
Superoxide Anion ◽  
Defense Mechanisms ◽  
Immune Defense ◽  
Polymorphonuclear Neutrophils ◽  
Ethanol Administration ◽  
Ethanol Intoxication ◽  
Phagocytic Cells

Bacterial endotoxins [lipopolysaccharide (LPS)] are potent immunomodulators, and ethanol is known to depress certain immune defense mechanisms. Thus the combined impact of these two agents on the generation of superoxide anion (O2(-).) by isolated hepatic phagocytic cells was investigated. Ethanol was infused intravenously into rats for 7 h, and Escherichia coli LPS was injected intravenously at 4 h after ethanol administration. Control groups received an equal volume of saline or ethanol alone. Nonparenchymal cells that were composed of endothelial and Kupffer cells and few polymorphonuclear neutrophils (PMN; less than 1%) were obtained after collagenase-pronase digestion. In the LPS-treated rats, the total number of PMN per liver increased significantly. Histological sections of the liver showed PMN infiltration and areas of necrosis after LPS treatment with or without ethanol. In the presence of either phorbol 12-myristate 13-acetate or opsonized zymosan in vitro, Kupffer cells and hepatic PMN from LPS-treated rats generated large amounts of O2(-).. Ethanol intoxication in vitro by these cells to 50%. Ethanol alone (without LPS) had no effect on the production of O2(-).. These studies demonstrate that ethanol intoxication was associated with the downregulation of the LPS-enhanced in vivo priming of hepatic phagocytes to generate O2(-). in vitro and may thus contribute to the enhanced susceptibility of alcoholic subjects to develop an infection.

scholarly journals Control of Neutrophil activation through Semaphorin 7A-Plexin C1 is essential for immune defense during pulmonary sepsis.

2021 ◽  
Author(s):  
Peter Rosenberger ◽  
Tiago Granja
Keyword(s):  
Early Phase ◽  
Defense Mechanisms ◽  
Neutrophil Migration ◽  
Serum Levels ◽  
Neutrophil Activation ◽  
Immune Defense ◽  
And Function ◽  
Neutrophil Surface

Pulmonary defense mechanisms are critical for host integrity during the early phase of pneumonia and sepsis. These processes are fundamentally dependent on the activation of neutrophils during the early phase of the innate immune response. Recent work has shown that semaphorin 7A (Sema7A) holds significant impact on platelet activation, yet its role in neutrophil migration and function is not well known. We report here that Sema7A binds to neutrophil PlexinC1, increasing integrins and L-selectin on the neutrophil surface. Sema7A-induced neutrophil activation also prompted neutrophil chemotaxis in vitro and the formation of platelet-neutrophil complexes in vivo. We also observed altered adhesion and transmigration of neutrophils in Sema7A-/- animals in the lung. Sema7A-/- animals also showed altered crawling properties of neutrophils. This resulted in increased number of neutrophils in the interstitial space of Sema7A-/- animals but reduced numbers of neutrophils in the alveolar space during pneumonia-induced pulmonary sepsis. This was associated with significantly worse outcome of Sema7A-/- animals in a model of Klebsiella pneumoniae. Furthermore, we were able to show a correlation between serum levels of Sema7A in patients with ARDS and oxygenation levels. Thus, we show here that Sema7A has an immunomodulatory effect though which might influence patient outcome during pulmonary sepsis.

scholarly journals Viral Determinants of Resistance to Treatment in Patients with Hepatitis C

2007 ◽  
Vol 20 (1) ◽  
pp. 23-38 ◽  
Author(s):  
Anette Wohnsland ◽  
Wolf Peter Hofmann ◽  
Christoph Sarrazin
Keyword(s):  
Hepatitis C ◽  
Antiviral Therapy ◽  
Phase 1 ◽  
Treatment Success ◽  
Antiviral Agents ◽  
Antiviral Drugs ◽  
Immune Defense ◽  
Phenotypic Resistance

SUMMARY Chronic hepatitis C virus (HCV) infection affects more than 170 million persons worldwide and is responsible for the development of liver cirrhosis in many cases. Standard treatment with pegylated alpha interferon (IFN-α) in combination with the nucleoside analogue ribavirin leads to a sustained virologic response in approximately half of the patients. IFN-α is classified as an indirect treatment, as it interacts with the host's immune response. The mechanism of action of ribavirin is still unknown. The benefit of triple therapy by adding other antiviral agents, e.g., amantadine, is controversial. Currently, new direct antiviral drugs (HCV protease/polymerase inhibitors) are being evaluated in phase 1/phase 2 trials. Phenotypic resistance to antiviral therapy has been attributed to amino acid variations within distinct regions of the HCV polyprotein. While sensitivity to IFN-α-based antiviral therapy in vivo is clearly correlated with the number of mutations within the HCV NS5A protein, the underlying functional mechanisms for this association are unknown. In turn, in vitro, several mechanisms to circumvent the host immune defense or to block treatment-induced antiviral activities have been described for different HCV proteins. By the introduction of direct antiviral drugs, hepatitis C therapy now is entering a new era in which the development of resistance may become the most important parameter for treatment success or failure.

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