scholarly journals High Dimensional Immune Profiling Reveals Different Response Patterns in Active and Latent Tuberculosis Following Stimulation With Mycobacterial Glycolipids

2021 ◽  
Vol 12 ◽  
Author(s):  
Carolina S. Silva ◽  
Christopher Sundling ◽  
Elin Folkesson ◽  
Gabrielle Fröberg ◽  
Claudia Nobrega ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Envelope ◽  
Latent Tuberculosis ◽  
Phosphatidyl Inositol ◽  
Antigen Presenting Cells ◽  
Clear Understanding ◽  
Effective Response ◽  
Ifn Γ ◽  
Different Response ◽  
Antigen Presenting

Upon infection with Mycobacterium tuberculosis (Mtb) the host immune response might clear the bacteria, control its growth leading to latent tuberculosis (LTB), or fail to control its growth resulting in active TB (ATB). There is however no clear understanding of the features underlying a more or less effective response. Mtb glycolipids are abundant in the bacterial cell envelope and modulate the immune response to Mtb, but the patterns of response to glycolipids are still underexplored. To identify the CD45+ leukocyte activation landscape induced by Mtb glycolipids in peripheral blood of ATB and LTB, we performed a detailed assessment of the immune response of PBMCs to the Mtb glycolipids lipoarabinomannan (LAM) and its biosynthetic precursor phosphatidyl-inositol mannoside (PIM), and purified-protein derivate (PPD). At 24 h of stimulation, cell profiling and secretome analysis was done using mass cytometry and high-multiplex immunoassay. PIM induced a diverse cytokine response, mainly affecting antigen-presenting cells to produce both pro-inflammatory and anti-inflammatory cytokines, but not IFN-γ, contrasting with PPD that was a strong inducer of IFN-γ. The effect of PIM on the antigen-presenting cells was partly TLR2-dependent. Expansion of monocyte subsets in response to PIM or LAM was reduced primarily in LTB as compared to healthy controls, suggesting a hyporesponsive/tolerance pattern derived from Mtb infection.

scholarly journals Stimulation with mycobacterial glycolipids and PPD reveals different innate immune response profiles in active and latent TB

2021 ◽  
Author(s):  
Carolina S Silva ◽  
Christopher Sundling ◽  
Elin Folkeson ◽  
Gabrielle Fröberg ◽  
Claudia Nobrega ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Envelope ◽  
Latent Tuberculosis ◽  
Phosphatidyl Inositol ◽  
Clear Understanding ◽  
Effective Response ◽  
Gm Csf ◽  
Detailed Assessment ◽  
Ifn Γ ◽  
Antigen Presenting

AbstractUpon infection with Mycobacterium tuberculosis (Mtb) the host immune response might clear the bacteria, control its growth leading to latent tuberculosis (LTB), or fail to control its growth resulting in active TB (ATB). There is however no clear understanding of the features underlying a more or less effective response. Mtb glycolipids are abundant in the bacterial cell envelope and modulate the immune response to Mtb, but the patterns of response to glycolipids are still underexplored. To identify the CD45+ leukocyte activation landscape induced by Mtb glycolipids in peripheral blood of ATB and LTB, we performed a detailed assessment of the immune response of PBMCs to the Mtb glycolipids lipoarabinomannan (LAM) and its biosynthetic precursor phosphatidyl-inositol mannoside (PIM), and PPD. At 24 h and 5 days of stimulation, cell profiling and secretome analysis was done using mass cytometry and high-multiplex immunoassay. PIM mainly affected antigen-presenting cells to produce both proinflammatory (IL-2, IL-6, IL-17A, TNF-α and GM-CSF), and IL-4 and IL-10 cytokines, but not IFN-γ. LAM triggered a similar, albeit weaker, response. By contrast, PPD induced an increase in IFN-γ-producing cells. Moreover, PPD also led to increased numbers of IL-2, IL-6, IL-10, IL-17A, TNF-α and GrzB-producing cells. Treatment with an anti-TLR2 antibody led to partial inhibition of PIM-induced IL-6 production in myeloid cells, suggesting that PIM induces IL-6 production through TLR2. Expansion of monocyte subsets in response to PIM or LAM was reduced in both ATB and LTB as compared to healthy controls, suggesting a hyporesponsive/tolerance pattern in Mtb-infected individuals.

The Hexavalent CD40 Agonist HERA-CD40L Induces T-Cell–mediated Antitumor Immune Response Through Activation of Antigen-presenting Cells

2018 ◽  
Vol 41 (9) ◽  
pp. 385-398 ◽  
Author(s):  
Christian Merz ◽  
Jaromir Sykora ◽  
Viola Marschall ◽  
David M. Richards ◽  
Karl Heinonen ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cell ◽  
Antigen Presenting Cells ◽  
Antitumor Immune Response ◽  
Antigen Presenting

scholarly journals In vivo role of IFN-γ produced by antigen-presenting cells in early host defense against intracellular pathogens

2003 ◽  
Vol 33 (10) ◽  
pp. 2666-2675 ◽  
Author(s):  
Kazutomo Suzue ◽  
Takashi Asai ◽  
Tsutomu Takeuchi ◽  
Shigeo Koyasu
Keyword(s):  
Host Defense ◽  
Antigen Presenting Cells ◽  
Intracellular Pathogens ◽  
Ifn Γ ◽  
Antigen Presenting

The use of HLA-A*0201-transfected K562 as standard antigen-presenting cells for CD8+ T lymphocytes in IFN-γ ELISPOT assays

2002 ◽  
Vol 259 (1-2) ◽  
pp. 95-110 ◽  
Author(s):  
Cedrik M Britten ◽  
Ralf G Meyer ◽  
Tanja Kreer ◽  
Ingo Drexler ◽  
Thomas Wölfel ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Antigen Presenting Cells ◽  
Cd8 T Lymphocytes ◽  
Ifn Γ ◽  
Antigen Presenting

scholarly journals Cathepsin B in Antigen-Presenting Cells Controls Mediators of the Th1 Immune Response during Leishmania major Infection

2014 ◽  
Vol 8 (9) ◽  
pp. e3194 ◽  
Author(s):  
Iris J. Gonzalez-Leal ◽  
Bianca Röger ◽  
Angela Schwarz ◽  
Tanja Schirmeister ◽  
Thomas Reinheckel ◽  
...  
Keyword(s):  
Immune Response ◽  
Cathepsin B ◽  
Leishmania Major ◽  
Antigen Presenting Cells ◽  
Major Infection ◽  
Antigen Presenting ◽  
Th1 Immune Response

scholarly journals Sensitivity of Dendritic Cells to Microenvironment Signals

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Juliana Maria Motta ◽  
Vivian Mary Rumjanek
Keyword(s):  
Immune Response ◽  
Dendritic Cells ◽  
Tumor Growth ◽  
Functional Status ◽  
Organ Transplantation ◽  
Immune Tolerance ◽  
Antigen Presenting Cells ◽  
Lessons Learned ◽  
Antigen Presenting ◽  
The Way

Dendritic cells are antigen-presenting cells capable of either activating the immune response or inducing and maintaining immune tolerance. They do this by integrating stimuli from the environment and changing their functional status as a result of plasticity. The modifications suffered by these cells have consequences in the way the organism may respond. In the present work two opposing situations known to affect dendritic cells are analyzed: tumor growth, leading to a microenvironment that favors the induction of a tolerogenic profile, and organ transplantation, which leads to a proinflammatory profile. Lessons learned from these situations may help to understand the mechanisms of modulation resulting not only from the above circumstances, but also from other pathologies.

Long-Term Phenotypic Correction of Hemophilia A Mice Following Intravenous Injection of miRNA-Regulated Lentiviral Vectors.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2587-2587
Author(s):  
Hideto Matsui ◽  
Margareth Ozelo ◽  
Carol Hegadorn ◽  
Andrea Labelle ◽  
Erin Burnett ◽  
...  
Keyword(s):  
Immune Response ◽  
Intravenous Injection ◽  
Hemophilia A ◽  
Lentiviral Vector ◽  
Therapeutic Potential ◽  
Antigen Presenting Cells ◽  
Lentiviral Vectors ◽  
Target Sequence ◽  
Antigen Presenting

Abstract Hemophilia A is an excellent candidate disorder for the use of gene therapy as a treatment modality. To date, although lentiviral delivery of the factor VIII (FVIII) transgene has the potential to provide sustained therapeutic correction of the hemophilia A phenotype, this has not been achieved in adult animals because of the anti-FVIII immune response. We have used lentiviral vectors to deliver the canine FVIII transgene to hemophilia A neonates and although no anti-FVIII immune response occurred, and indeed the treated mice displayed long-term tolerance to the canine FVIII antigen, this strategy did not provide sustained therapeutic levels of plasma FVIII. To overcome these limitations, we modified our lentiviral vector and the protocol for viral delivery to enhance transduction of hepatocytes and direct transgene expression away from antigen presenting cells. We engineered lentiviral vectors that encode the B-domain deleted canine FVIII cDNA under the transcriptional control of either a non-viral ubiquitous promoter or two different liver-restricted promoters. However, no plasma FVIII was detected in any of the adult hemophilia A mice after intravenous injection of the various lentiviral vectors because of an anti-canine FVIII immune response. An alternate pseudotype (GP64) was used to enhance transduction of hepatocytes and a target sequence for a hematopoietic-specific microRNA was incorporated into the transgene to prevent FVIII expression in antigen presenting cells that may arise from promoter trapping. When hemophilia A mice received intravenous infusions of these modified vectors, where the cFVIII trangene is under the control of either of the liver-restricted promoters, all treated mice (n=4) showed sustained FVIII expression (mean FVIII levels 28.2±2.4 mU/mL) for more than 150 days (last time analyzed) without developing anti-FVIII antibodies. Moreover, temporary depletion of Kuppfer cells prior to viral administration resulted in a 3-fold elevation of levels of plasma FVIII (mean FVIII levels 83.3±2.1mU/mL; n=4). Analysis of the biodistribution of the integrated FVIII transgene and expression of canine FVIII mRNA indicate an enhanced restriction of FVIII expression in hepatocytes with the use of the modified lentiviral vectors. These results demonstrate, for the first time, the long-term therapeutic potential of modified lentiviral vectors for treating adult pre-clinical animal models of hemophilia A.

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