scholarly journals Irradiation Does Not Compromise or Exacerbate the Innate Immune Response in the Brains of Mice That Were Transplanted with Bone Marrow Stem Cells

Stem Cells ◽  
2007 ◽  
Vol 25 (12) ◽  
pp. 3165-3172 ◽  
Author(s):  
Nicolas P. Turrin ◽  
Marie-Michèle Plante ◽  
Martine Lessard ◽  
Serge Rivest
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Immune Response ◽  
Innate Immune Response ◽  
Bone Marrow Stem Cells ◽  
Innate Immune

scholarly journals The Regulation of the CNS Innate Immune Response Is Vital for the Restoration of Tissue Homeostasis (Repair) after Acute Brain Injury: A Brief Review

2010 ◽  
Vol 2010 ◽  
pp. 1-18 ◽  
Author(s):  
M. R. Griffiths ◽  
P. Gasque ◽  
J. W. Neal
Keyword(s):  
Stem Cells ◽  
Immune Response ◽  
T Cell ◽  
Innate Immune Response ◽  
T Cell Activation ◽  
Cell Activation ◽  
Tissue Homeostasis ◽  
Innate Immune ◽  
Apoptotic Cells ◽  
Treg Population

Neurons and glia respond to acute injury by participating in the CNS innate immune response. This involves the recognition and clearance of “not self ” pathogens and “altered self ” apoptotic cells. Phagocytic receptors (CD14, CD36, TLR–4) clear “not self” pathogens; neurons and glia express “death signals” to initiate apoptosis in T cells.The complement opsonins C1q, C3, and iC3b facilitate the clearance of apoptotic cells by interacting with CR3 and CR4 receptors. Apoptotic cells are also cleared by the scavenger receptors CD14, Prs-R, TREM expressed by glia. Serpins also expressed by glia counter the neurotoxic effects of thrombin and other systemic proteins that gain entry to the CNS following injury. Complement pathway and T cell activation are both regulated by complement regulatory proteins expressed by glia and neurons. CD200 and CD47 are NIRegs expressed by neurons as “don't eat me” signals and they inhibit microglial activity preventing host cell attack. Neural stem cells regulate T cell activation, increase the Treg population, and suppress proinflammatory cytokine expression. Stem cells also interact with the chemoattractants C3a, C5a, SDF-1, and thrombin to promote stem cell migration into damaged tissue to support tissue homeostasis.

scholarly journals Innate Immune Response of Human Embryonic Stem Cell-Derived Fibroblasts and Mesenchymal Stem Cells to Periodontopathogens

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Gopu Sriram ◽  
Vaishali Prakash Natu ◽  
Intekhab Islam ◽  
Xin Fu ◽  
Chaminda Jayampath Seneviratne ◽  
...  
Keyword(s):  
Stem Cells ◽  
Immune Response ◽  
Mesenchymal Stem Cells ◽  
Innate Immune Response ◽  
Embryonic Stem ◽  
Innate Immune ◽  
Microbial Pathogens ◽  
Multipotent Stem Cells ◽  
Cytokine Expression Profile ◽  
The Impact

Periodontitis involves complex interplay of bacteria and host immune response resulting in destruction of supporting tissues of the tooth. Toll-like receptors (TLRs) play a role in recognizing microbial pathogens and eliciting an innate immune response. Recently, the potential application of multipotent stem cells and pluripotent stem cells including human embryonic stem cells (hESCs) in periodontal regenerative therapy has been proposed. However, little is known about the impact of periodontopathogens on hESC-derived progenies. This study investigates the effects of heat-killed periodontopathogens, namely,Porphyromonas gingivalisandAggregatibacter actinomycetemcomitans, on TLR and cytokine expression profile of hESC-derived progenies, namely, fibroblasts (hESC-Fib) and mesenchymal stem cells (hESC-MSCs). Additionally, the serotype-dependent effect ofA. actinomycetemcomitanson hESC-derived progenies was explored. Both hESC-Fib and hESC-MSCs constitutively expressedTLR-2andTLR-4. hESC-Fib upon exposure to periodontopathogens displayed upregulation of TLRs and release of cytokines (IL-1β, IL-6, and IL-8). In contrast, hESC-MSCs were largely nonresponsive to bacterial challenge, especially in terms of cytokine production. Further, exposure of hESC-Fib toA. actinomycetemcomitansserotype c was associated with higher IL-8 production than serotype b. In contrast, the hESC-MSCs displayed no serotype-dependent response. Differential response of the two hESC progenies implies a phenotype-dependent response to periodontopathogens and supports the concept of immunomodulatory properties of MSCs.

scholarly journals Hematopoietic Stem and Progenitor Cells as Effectors in Innate Immunity

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Jennifer L. Granick ◽  
Scott I. Simon ◽  
Dori L. Borjesson
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Progenitor Cells ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Phenotypic Characterization ◽  
Hematopoietic Stem ◽  
Effector Cells ◽  
Stem And Progenitor Cells ◽  
And Function

Recent research has shed light on novel functions of hematopoietic stem and progenitor cells (HSPC). While they are critical for maintenance and replenishment of blood cells in the bone marrow, these cells are not limited to the bone marrow compartment and function beyond their role in hematopoiesis. HSPC can leave bone marrow and circulate in peripheral blood and lymph, a process often manipulated therapeutically for the purpose of transplantation. Additionally, these cells preferentially home to extramedullary sites of inflammation where they can differentiate to more mature effector cells. HSPC are susceptible to various pathogens, though they may participate in the innate immune response without being directly infected. They express pattern recognition receptors for detection of endogenous and exogenous danger-associated molecular patterns and respond not only by the formation of daughter cells but can themselves secrete powerful cytokines. This paper summarizes the functional and phenotypic characterization of HSPC, their niche within and outside of the bone marrow, and what is known regarding their role in the innate immune response.

scholarly journals Role of the Thrombin-PAR-1 Pathway in Coxsackievirus Induced Hepatitis

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1470-1470
Author(s):  
Kohei Tatsumi ◽  
Silvio Antoniak ◽  
Nigel Mackman
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Primary Mouse Hepatocytes ◽  
Primary Mouse ◽  
Mouse Hepatocytes ◽  
Transplantation Experiments

Abstract Objective: Coxsackievirus B3 (CVB3) can infect different tissues including the heart and liver. Recently, we found that activation of the coagulation cascade and protease-activated receptor 1 (PAR-1) enhances toll-like receptor-3 (TLR3) mediated interferon-β (IFN-β) expression and protects mice from CVB3-induced myocarditis. Here, we investigated the role of PAR-1 in early anti-viral responses in mice and isolated hepatocytes. Methods: Wild-type (WT) and PAR-1 deficient (PAR-1-/-) mice were infected with CVB3 intraperitoneally. The innate immune response, viral load, liver enzyme plasma levels, and inflammation levels were analyzed. Bone-marrow transplantation experiments with the combination of WT mice PAR-1-/- mice were performed to identify the cellular source of PAR-1 contributing to the innate immune response to CVB3. We also analyzed the effect of the direct thrombin inhibition with dabigatran etexilate on CVB3 hepatitis. In addition, we analyzed the effect of PAR-1 activation on TLR3-dependent interferon (IFN)-β expression in primary mouse hepatocytes and the human hepatocyte cell line PH5CH8 in vitro. Results: PAR-1-/- mice exhibited a reduced early innate immune response in the liver at day 4 after infection, which was associated at later times (day 8) to higher viral titers in the liver, increased alanine transaminase plasma levels and more remarkable inflammation compared to control WT mice. Bone marrow transplantation experiments demonstrated that PAR-1 on non-hematopoietic played the major role in the innate immune response of CVB3 hepatitis. Stimulation of PAR-1 with either thrombin or agonist peptide on primary mouse hepatocytes and human PH5CH8 cells in vitro enhanced the antiviral response to dsRNA by increasing IFN-β and C-X-C motif chemokine 10 (CXCL10) expressions, supporting the results of in vivo experiments. Conclusion: Our results suggest that activation of PAR-1 on hepatocytes enhances the innate immune response to CVB3 in the liver. Disclosures No relevant conflicts of interest to declare.

scholarly journals Global Proteomic and Methylome Analysis in Human Induced Pluripotent Stem Cells Reveals Overexpression of a Human TLR3 Affecting Proper Innate Immune Response Signaling

Stem Cells ◽  
2019 ◽  
Vol 37 (4) ◽  
pp. 476-488 ◽  
Author(s):  
Jordi Requena ◽  
Ana Belen Alvarez-Palomo ◽  
Montserrat Codina-Pascual ◽  
Raul Delgado-Morales ◽  
Sebastian Moran ◽  
...  
Keyword(s):  
Stem Cells ◽  
Immune Response ◽  
Induced Pluripotent Stem Cells ◽  
Innate Immune Response ◽  
Pluripotent Stem Cells ◽  
Innate Immune ◽  
Methylome Analysis ◽  
Induced Pluripotent

Innate immune response to human bone marrow fibroblastic cell implantation in CB17 scid/beige mice

2006 ◽  
Vol 98 (4) ◽  
pp. 966-980 ◽  
Author(s):  
Zhidao Xia ◽  
Philip R. Taylor ◽  
Rachel M. Locklin ◽  
Siamon Gordon ◽  
Zhanfeng Cui ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Fibroblastic Cell ◽  
Cell Implantation

Aberrant Overexpression Of CD14 In Granulocytes Sensitizes Innate Immune Response In mDia1 Heterozygous Myelodysplastic Syndromes

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1557-1557
Author(s):  
Ganesan Keerthivasan ◽  
Baobing Zhao ◽  
Chad E Harris ◽  
Ling Zhang ◽  
Juehua Gao ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Innate Immune Response ◽  
Myelodysplastic Syndromes ◽  
Knockout Mice ◽  
Actin Polymerization ◽  
Conflicts Of Interest ◽  
Innate Immune ◽  
Increased Risk ◽  
A Cell

Abstract The myelodysplastic syndromes (MDS) are a group of pre-leukemic diseases characterized by increased risk of acute myeloid leukemia (AML). Heterozygous loss of chromosome 5q (5q-) is the most common cytogenetic abnormality in MDS. DIAPH1 is localized to 5q31 and encodes one of the formin family proteins, mDia1, involved in the regulation of linear actin polymerization. Mice with mDia1 deficiency develop hematologic features mimicking human myeloproliferative neoplasm, but its role in the pathogenesis of MDS is unclear. Here we report that mDia1 is largely dispensable for normal hematopoiesis. However, the committed or mature granulocytes in mDia1 heterozygous and knockout mice were activated and showed increased actin polarization. Strikingly, CD14 was aberrantly overexpressed in the bone marrow and peripheral granulocytes of mDia1 heterozygous and knockout mice in a cell-autonomous manner, leading to a hypersensitivity of the innate immune response to lipopolysaccharide (LPS) stimuli through CD14-Toll like receptor 4 (TLR4) signaling. Chronic stimulation with LPS accelerated the occurrence of MDS in mDia1 heterozygous and knockout mice. Similar findings of CD14 overexpression were observed in the bone marrow granulocytes of 5q- MDS patients, but not normal patients or MDS patients without 5q deletion. These patients exhibited relatively frequent infections with long duration of disease. Mechanistically, mDia1 was required for the endocytosis of CD14 upon LPS stimulation. Heterozygosity and loss of mDia1 led to diminished interferon expression that is dependent on CD14 endocytosis. Thus, our study revealed an essential role of the innate immune signaling in the pathogenesis of 5q- MDS. Specifically, heterozygosity or loss of mDia1 leads to a cell autonomous hypersensitivity of innate immune system in the granulocytes that causes myeloid dysplasia. Together with previous reported evidence of dyserythropoiesis due to loss of RPS14, and dysmegakaryopoiesis due to loss of mir-145/146a, these data fully recapitulate the pathogenesis of tri-lineage dysplasia in 5q- MDS. In addition, our study highlighted the significance of the activated CD14/TLR signaling pathway in the pathogenesis of MDS, which could serve as a novel target for therapeutic management. Disclosures: No relevant conflicts of interest to declare.

scholarly journals CD38 Controls the Innate Immune Response against Listeria monocytogenes

2013 ◽  
Vol 81 (11) ◽  
pp. 4091-4099 ◽  
Author(s):  
Timo Lischke ◽  
Kira Heesch ◽  
Valéa Schumacher ◽  
Michael Schneider ◽  
Friedrich Haag ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Immune Response ◽  
Listeria Monocytogenes ◽  
Innate Immune Response ◽  
Cell Activation ◽  
Cell Types ◽  
Innate Immune ◽  
Infection Model ◽  
Content Type ◽  
Inflammatory Monocytes

ABSTRACTCD38, adenosine-5′-diphosphate-ribosyl cyclase 1, is a multifunctional enzyme, expressed on a wide variety of cell types. CD38 has been assigned diverse functions, including generation of calcium-mobilizing metabolites, cell activation, and chemotaxis. Using a murineListeria monocytogenesinfection model, we found that CD38 knockout (KO) mice were highly susceptible to infection. Enhanced susceptibility was already evident within 3 days of infection, suggesting a function of CD38 in the innate immune response. CD38 was expressed on neutrophils and inflammatory monocytes, and especially inflammatory monocytes further upregulated CD38 during infection. Absence of CD38 caused alterations of the migration pattern of both cell types to sites of infection. We observed impaired accumulation of cells in the spleen but surprisingly similar or even higher accumulation of cells in the liver. CD38 KO and wild-type mice showed similar changes in the composition of neutrophils and inflammatory monocytes in blood and bone marrow, indicating that mobilization of these cells from the bone marrow was CD38 independent.In vitro, macrophages of CD38 KO mice were less efficient in uptake of listeria but still able to kill the bacteria. Dendritic cells also displayed enhanced CD38 expression following infection. However, absence of CD38 did not impair the capacity of mice to prime CD8+T cells againstL. monocytogenes, and CD38 KO mice could efficiently control secondary listeria infection. In conclusion, our results demonstrate an essential role for CD38 in the innate immune response againstL. monocytogenes.

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