Search results for "Innate"
showing 10 items of 638 documents
Idelalisib Impairs TREM-1 and TLR Mediated Neutrophil Activation
2016
Abstract Introduction: Polymorphonuclear neutrophils (PMN) play an essential role in innate inflammatory processes. Their functions are strictly regulated and many activating / inhibiting mechanisms along with their pathways are only incompletely understood. Besides toll-like receptors (TLR) and NOD-like receptors (NLR), triggering receptor expressed on myeloid cells (TREM)-1 is implicated in innate immune activation of these cells and plays a role in infectious as well as non-infectious conditions. Activation of TREM-1 results in release of pro-inflammatory chemokines and cytokines, increased surface expression of cell activation markers and degranulation. In TREM-1 downstream pathways and…
Tick Salivary Sialostatin L Represses the Initiation of Immune Responses by Targeting IRF4-Dependent Transcription in Murine Mast Cells
2015
Abstract Coevolution of ticks and the vertebrate immune system has led to the development of immunosuppressive molecules that prevent immediate response of skin-resident immune cells to quickly fend off the parasite. In this article, we demonstrate that the tick-derived immunosuppressor sialostatin L restrains IL-9 production by mast cells, whereas degranulation and IL-6 expression are both unaffected. In addition, the expression of IL-1β and IRF4 is strongly reduced in the presence of sialostatin L. Correspondingly, IRF4- or IL-1R–deficient mast cells exhibit a strong impairment in IL-9 production, demonstrating the importance of IRF4 and IL-1 in the regulation of the Il9 locus in mast cel…
Development, Differentiation, and Diversity of Innate Lymphoid Cells
2014
Recent years have witnessed the discovery of an unprecedented complexity in innate lymphocyte lineages, now collectively referred to as innate lymphoid cells (ILCs). ILCs are preferentially located at barrier surfaces and are important for protection against pathogens and for the maintenance of organ homeostasis. Inappropriate activation of ILCs has been linked to the pathogenesis of inflammatory and autoimmune disorders. Recent evidence suggests that ILCs can be grouped into two separate lineages, cytotoxic ILCs represented by conventional natural killer (cNK) cells and cytokine-producing helper-like ILCs (i.e., ILC1s, ILC2s, ILC3s). We will focus here on current work in humans and mice th…
Dendritic cell-derived IL-12p40 homodimer contributes to susceptibility in cutaneous leishmaniasis in BALB/c mice
2007
Abstract Protection against Leishmania major in resistant C57BL/6 mice is mediated by Th1 cells, whereas susceptibility in BALB/c mice is the result of Th2 development. IL-12 release by L. major-infected dendritic cells (DC) is critically involved in differentiation of Th1 cells. Previously, we reported that strain differences in the production of DC-derived factors, e.g., IL-1αβ, are in part responsible for disparate disease outcome. In the present study, we analyzed the release of IL-12 from DC in more detail. Stimulated DC from C57BL/6 and BALB/c mice released comparable amounts of IL-12p40 and p70. In the absence of IL-4, BALB/c DC produced significantly more IL-12p40 than C57BL/6 DC. D…
Regulatory T Cells More Effectively Suppress Th1-Induced Airway Inflammation Compared with Th2
2011
Abstract Asthma is a syndrome with different inflammatory phenotypes. Animal models have shown that, after sensitization and allergen challenge, Th2 and Th1 cells contribute to the development of allergic airway disease. We have previously demonstrated that naturally occurring regulatory T cells (nTregs) can only marginally suppress Th2-induced airway inflammation and airway hyperresponsiveness. In this study, we investigated nTreg-mediated suppression of Th2-induced and Th1-induced acute allergic airway disease. We demonstrate in vivo that nTregs exert their suppressive potency via cAMP transfer on Th2- and Th1-induced airway disease. A comparison of both phenotypes revealed that, despite …
EVOLUTION OF THE INNATE AND ADAPTIVE IMMUNE SYSTEMS
1999
Porifera (sponge) form the lowest metazoan phylum and share a common ancestor with other metazoan phyla. In the present study, it is reported that sponges possess molecules that are similar in structure to those molecules involved in the immune system in mammals. Experiments with the marine sponges Geodia cydonium and Suberites domuncula have been performed on tissue (auto- and allografting) as well as on a cellular level. The studies revealed that sponges are provided with elements of the mammalian innate immune system, such as molecules containing scavenger receptor cysteine-rich domains. Furthermore, macrophage-derived cytokine-like molecules have been identified that are up-regulated du…
Human genetic polymorphisms and risk of viral infection after solid organ transplantation.
2021
The immune system plays a key role in the host defense against viral pathogens. A signaling cascade is activated upon infection involving a variety of molecules such as pattern-recognition receptors (PRRs), interleukins or antiviral interferons. Long-term immunosuppression after solid organ transplantation (SOT) mainly abrogates adaptive T-cell-mediated responses, thus highlighting the relative contribution of innate immunity. Single-nucleotide polymorphisms (SNPs) within genes coding for PRRs or soluble mediators have been associated with differential susceptibility to viral infections among SOT recipients. A protective effect against cytomegalovirus (CMV) infection or disease has been att…
A Method of Transposon Insertion Sequencing in Comprehensively Identifying Vibrio vulnificus Genes Required for Growth in Human Serum
2021
One of the most powerful approaches to detect the loci that enable a pathogen to cause disease is the creation of a high-density transposon mutant library by transposon insertion sequencing (TIS) and the screening of the library using an adequate in vivo and/or ex vivo model of the disease. Here we describe the procedure for detection of the putative loci required for a septicemic pathogen to cause sepsis in humans by using TIS plus an ex vivo model of septicaemia: to grow the pathogen in fresh and inactivated human serum. We selected V. vulnificus because it is a highly invasive pathogen capable of spreading from an infection site to the bloodstream, causing sepsis and death in less than 2…
Finnish salmon resistant to Gyrodactylus salaris: a long-term study at fish farms.
1996
Abstract The occurrence of Gyrodactylus salaris on Baltic salmon ( Salmo salar ), sea trout ( S. trutta m. trutta ) and brown trout ( S. trutta m. lacustris ) was examined from 1984 to 1993 at 4 fish farms (A, B, C and D) that produce smolts for stocking in northern Finland. No G. salaris was found on the sea or brown trout, but it did occur on salmon for 6–7 years at farms B, C and D, the prevalences of infection being 9.5%, 17.7% and 8.8% for salmon yearlings and smolts during that time, respectively, but less than 1.2% for fingerlings at farms B and C. Only brood stock salmon were infected at farm A in 4 years. The abundances of G. salaris increased during the second winter of each year …
IL-4 depletion enhances host resistance and passive IgA protection against tuberculosis infection in BALB/c mice.
2007
The influence of Th2 cytokines in tuberculosis has been a matter of dispute. Here we report that IL-4 has a profound regulatory effect on the infection of BALB/c mice with Mycobacterium tuberculosis. Depletion of IL-4 with a neutralizing mAb caused only evanescent reduction of lung infection, but when combined with i.n. inoculations of IgA anti-mycobacterial alpha-crystallin mAb and mouse rIFN-gamma, we observed a 40-fold reduction of the bacterial counts in the lungs at 3 wks following i.n. infection (p<0.001). In genetically deficient IL-4-/- BALB/c mice, infection in both lung and spleen was substantially reduced for up to 8 wks without further treatment. Reconstitution of IL-4-/- mice w…