scholarly journals Antibody-based vaccine for tuberculosis: validation in horse foals challenged with the TB-related pathogen Rhodococcus equi

2018 ◽  
Author(s):  
C. Cywes-Bentley ◽  
J. N. Rocha ◽  
A. I. Bordin ◽  
M. Vinacur ◽  
S. Rehman ◽  
...  
Keyword(s):  
Severe Pneumonia ◽  
Surface Expression ◽  
Interferon Γ ◽  
Rhodococcus Equi ◽  
Intracellular Pathogens ◽  
Severe Respiratory Distress ◽  
Antibody Recognition ◽  
Immune Correlates ◽  
Vaccine Antigens ◽  
Surface Polysaccharide

AbstractImmune correlates for protection against Mycobacterium tuberculosis (Mtb) infection and other intracellular pathogens are largely undetermined. Whether there is a role for antibody-mediated immunity is controversial. Rhodococcus equi is an intracellular pathogen causing severe pneumonia in young horse foals, eliciting a disease with many similarities to TB including intracellular residence, formation of granulomas and induction of severe respiratory distress. No purified vaccine antigens exist for R. equi or Mtb infections. Both express the microbial surface polysaccharide antigen poly-N-acetyl glucosamine (PNAG). In a randomized, controlled, blinded challenge trial, vaccination of pregnant mares with a synthetic PNAG oligosaccharide conjugated to tetanus toxoid elicited antibody that transferred to foals via colostrum and provided nearly complete protection against R. equi pneumonia. Infusion of PNAG-hyperimmune plasma protected 100% of foals against R. equi pneumonia. Vaccination induced opsonic antibodies that killed extracellular and intracellular R. equi and other intracellular pathogens. Killing of intracellular organisms was dependent on antibody recognition of surface expression of PNAG on infected macrophages, complement deposition and PMN-assisted lysis of infected macrophages. Protection also correlated with PBMC release of interferon-γ in response to PNAG. Antibody-mediated opsonic killing and interferon-γ release in response to PNAG may protect against disease caused by intracellular bacterial pathogens.

scholarly journals Enhancement of tumoricidal activity of alveolar macrophages via CD40-CD40 ligand interaction

1999 ◽  
Vol 277 (1) ◽  
pp. L49-L57 ◽  
Author(s):  
Kazuyoshi Imaizumi ◽  
Tsutomu Kawabe ◽  
Satoshi Ichiyama ◽  
Hitoshi Kikutani ◽  
Hideo Yagita ◽  
...  
Keyword(s):  
Alveolar Macrophages ◽  
Cd40 Ligand ◽  
Surface Expression ◽  
Interferon Γ ◽  
Interleukin 12 ◽  
Cell Mediated Immunity ◽  
Ligand Interaction ◽  
Tumoricidal Activity ◽  
New Strategy ◽  
Factor Α

CD40-CD40 ligand (CD40L) interaction was originally defined as important molecules for the development of humoral immunity. Thereafter, some investigations have focused on its essential roles for the induction of cell-mediated immunity in host defenses. Here we investigated the antitumor activity of murine alveolar macrophages through CD40-CD40L interaction. The CD40L gene was transfected into murine lung cancer cells (3LLSA), and CD40L-expressing clones (3LLSA-CD40L) were established. Stimulation of CD40 molecules on the surface of alveolar macrophages with 3LLSA-CD40L cells induced the production of nitric oxide, tumor necrosis factor-α, and interleukin-12 and the tumoricidal activity of alveolar macrophages in the presence of interferon-γ, which increased the surface expression of CD40 molecules on alveolar macrophages. These findings were not observed when alveolar macrophages were obtained from CD40-deficient mice. On the other hand, interleukin-6 production by alveolar macrophages did not depend on CD40-CD40L interaction. We also established a murine melanoma cell line expressing CD40L (B16 4A5-CD40L) that could induce tumoricidal activity of alveolar macrophages. Furthermore, when spleen cells were cocultivated with 3LLSA-CD40L cells, specific cytotoxic T lymphocytes for wild-type 3LLSA cells could be induced. These results suggest that CD40L gene transfer into tumor cells may induce antitumor immunity in a tumor-bearing host and may offer a new strategy for cancer gene therapy.

Interferon-γ Upregulates CCR5 Expression in Cord and Adult Blood Mononuclear Phagocytes

Blood ◽  
1999 ◽  
Vol 93 (4) ◽  
pp. 1137-1144 ◽  
Author(s):  
Deepa Hariharan ◽  
Steven D. Douglas ◽  
Benhur Lee ◽  
Jian-Ping Lai ◽  
Donald E. Campbell ◽  
...  
Keyword(s):  
Cell Surface ◽  
Hiv Infection ◽  
Chemokine Receptors ◽  
Surface Expression ◽  
Interferon Γ ◽  
Mononuclear Phagocytes ◽  
Cell Surface Expression ◽  
Ccr5 Expression ◽  
Hiv Entry ◽  
Ifn Γ

Abstract The C-C chemokine receptors CCR5 and CCR3 are fusion coreceptors for human immunodeficiency virus (HIV) entry into macrophages. The regulation of their expression influences infectivity by HIV. We report here that interferon-γ (IFN-γ) a cytokine that has bidirectional effects on HIV infection of macrophages, significantly upregulated CCR5 and CCR3 cell surface expression in human mononuclear phagocytes isolated from placental cord blood and adult peripheral blood. Monocytes treated with IFN-γ showed increased chemotaxis to the CCR5 ligands macrophage inflammatory protein-1 (MIP-1) and MIP-1β, confirming the functional relevance of IFN-γ–induced CCR5 expression. However, IFN-γ suppressed HIV entry into macrophages. Interestingly, we demonstrated that IFN-γ inhibited cell surface expression of CD4, the major receptor for HIV. This finding may explain the suppressive effect of IFN-γ on HIV entry into macrophages, despite its enhancing effect on the expression of CCR5 and CCR3 by these cells. In addition, IFN-γ–induced secretion of C-C chemokines (RANTES, MIP-1, and MIP-1β) by mononuclear phagocytes may also suppress HIV entry into macrophages. These data provide further evidence for cytokine-mediated regulation of CCR5 expression and are consistent with a novel paradigm in which cytokines regulate HIV infection and leukocyte migration by reciprocal and opposing effects on the expression of CD4 and chemokine receptors.

Stimulation of toll-like receptor 4 expression in human mononuclear phagocytes by interferon-γ: a molecular basis for priming and synergism with bacterial lipopolysaccharide

Blood ◽  
2002 ◽  
Vol 99 (9) ◽  
pp. 3427-3431 ◽  
Author(s):  
Daniela Bosisio ◽  
Nadia Polentarutti ◽  
Marina Sironi ◽  
Sergio Bernasconi ◽  
Kensuke Miyake ◽  
...  
Keyword(s):  
Surface Expression ◽  
Interferon Γ ◽  
Mononuclear Phagocytes ◽  
Bacterial Lipopolysaccharide ◽  
Interleukin 12 ◽  
Mrna Levels ◽  
Adapter Protein ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Tlr4 Mrna

Abstract In human monocytes and macrophages, interferon-γ (IFNγ) augmented mRNA and surface expression of toll-like receptor 4 (TLR4), a crucial component of the signaling receptor complex for bacterial lipopolysaccharide (LPS). Expression of the accessory component MD-2 and of the adapter protein MyD88 was also increased. LPS increased TLR4 mRNA levels, but concomitantly decreased its surface expression. IFNγ counteracted the LPS-induced downregulation of TLR4. IFNγ-primed monocytes showed increased responsiveness to LPS in terms of phosphorylation of the interleukin-1 receptor–associated kinase (IRAK; immediately downstream of the MyD88 adapter protein), NF-kB DNA binding activity, and, accordingly, of cytokine (tumor necrosis factor α [TNFα] and interleukin-12 [IL-12]) production. These results suggest that enhanced TLR4 expression underlies the long-known priming by IFNγ of mononuclear phagocytes for pathogen recognition and killing as well as its synergism with LPS in macrophage activation.

From transcription to cell surface expression, the induction of MHC class II I-Aα by interferon-γ in macrophages is regulated at different levels

2001 ◽  
Vol 53 (2) ◽  
pp. 136-144 ◽  
Author(s):  
Martin Cullell-Young ◽  
Marta Barrachina ◽  
Carlos López-López ◽  
Eduard Goñalons ◽  
Jorge Lloberas ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mhc Class Ii ◽  
Surface Expression ◽  
Class Ii ◽  
Interferon Γ ◽  
Cell Surface Expression ◽  
Different Levels

scholarly journals Induction of Lectin-like Transcript 1 (LLT1) Protein Cell Surface Expression by Pathogens and Interferon-γ Contributes to Modulate Immune Responses

2011 ◽  
Vol 286 (44) ◽  
pp. 37964-37975 ◽  
Author(s):  
Claire Germain ◽  
Anders Meier ◽  
Teis Jensen ◽  
Perrine Knapnougel ◽  
Gwenola Poupon ◽  
...  
Keyword(s):  
Cell Surface ◽  
Immune Responses ◽  
Surface Expression ◽  
Interferon Γ ◽  
Cell Surface Expression ◽  
Protein Cell

Interferon-γ-induced PD-L1 surface expression on human oral squamous carcinoma via PKD2 signal pathway

Immunobiology ◽  
2012 ◽  
Vol 217 (4) ◽  
pp. 385-393 ◽  
Author(s):  
Jiao Chen ◽  
Yun Feng ◽  
Libing Lu ◽  
Hui Wang ◽  
Lina Dai ◽  
...  
Keyword(s):  
Squamous Carcinoma ◽  
Surface Expression ◽  
Interferon Γ ◽  
Signal Pathway ◽  
Oral Squamous Carcinoma

scholarly journals Systemic Steroid Treatment for Severe Expanding Pneumococcal Pneumonia

2015 ◽  
Vol 2015 ◽  
pp. 1-3
Author(s):  
Eran Lavi ◽  
David Shoseyov ◽  
Natalia Simanovsky ◽  
Rebecca Brooks
Keyword(s):  
Pneumococcal Pneumonia ◽  
Randomized Trials ◽  
Unusual Case ◽  
Severe Pneumonia ◽  
Supplemental Oxygen ◽  
Community Acquired Pneumonia ◽  
Systemic Steroid ◽  
Rapid Improvement ◽  
Severe Respiratory Distress ◽  
Potential Benefits

The treatment of bacterial community-acquired pneumonia (CAP) is based on appropriate antibiotic therapy and supportive care such as intravenous fluids and supplemental oxygen. There is no available data regarding the use of steroids in CAP in children. We present an unusual case of a child with severe respiratory distress, on the brink of mechanical ventilation, due to a rapidly expanding pneumococcal pneumonia. The administration of systemic steroids resulted in a dramatic response with rapid improvement of clinical and radiological abnormalities followed by improvement of laboratory abnormalities. This case report should raise the awareness of the potential benefits of steroids in the treatment of severe pneumonia in children. Prospective randomized trials are needed to confirm the efficacy of steroids in this setting and to determine which patients would benefit most from this.

scholarly journals Antibody Recognition of the Dengue Virus Proteome and Implications for Development of Vaccines

2011 ◽  
Vol 18 (4) ◽  
pp. 523-532 ◽  
Author(s):  
Stefan Fernandez ◽  
Emily D. Cisney ◽  
Alexander P. Tikhonov ◽  
Barry Schweitzer ◽  
Robert J. Putnak ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Vaccine Development ◽  
Rhesus Macaques ◽  
Protein Microarray ◽  
Vaccination Strategy ◽  
Antibody Responses ◽  
Wild Type ◽  
Antibody Recognition ◽  
Immune Correlates ◽  
The Tropics

ABSTRACTDengue is a mosquito-borne infection caused by four distinct serotypes of dengue virus, each appearing cyclically in the tropics and subtropics along the equator. Although vaccines are currently under development, none are available to the general population. One of the main impediments to the successful advancement of these vaccines is the lack of well-defined immune correlates of protection. Here, we describe a protein microarray approach for measuring antibody responses to the complete viral proteome comprised of the structural (capsid, membrane, and envelope) and nonstructural (NS1, NS2A, NS2B, NS3, NS4A, NS4B, and NS5) components of all four dengue virus serotypes (1 to 4). We examined rhesus macaques vaccinated with tetravalent vaccines consisting of live-attenuated virus (LAV) or purified inactivated virus (PIV), followed by boosting with LAV and challenging with wild-type dengue virus. We detected temporal increases in antibodies against envelope proteins in response to either vaccine, while only the PIV/LAV vaccination strategy resulted in anticapsid antibodies. In contrast to results from vaccination, naïve macaques challenged with wild-type viruses of each serotype demonstrated a balanced response to nonstructural and structural components, including responses against the membrane protein. Our results demonstrate discriminating details concerning the nature of antibody responses to dengue virus at the proteomic level and suggest the usefulness of this information for vaccine development.

scholarly journals One Case of Esophageal Obstruction Caused by Enteral Nutrition

2021 ◽  
Vol 2 (2) ◽  
Author(s):  
Yangzhong Wang ◽  
Xiuqing Liao ◽  
Xiaoli Bao ◽  
Xianlin Peng ◽  
Nan Tang
Keyword(s):  
Mechanical Ventilation ◽  
Enteral Nutrition ◽  
Sodium Bicarbonate ◽  
Nasogastric Tube ◽  
Gastric Tube ◽  
Foreign Bodies ◽  
Severe Pneumonia ◽  
Endoscopic Removal ◽  
Esophageal Obstruction ◽  
Severe Respiratory Distress

We report a case of complete esophageal obstruction caused by continuous enteral nutrition infusion via nasogastric tube. A 77 year old man received mechanical ventilation due to severe pneumonia and severe respiratory distress. He began using enteral nutrition emulsion (TPF) through a nasogastric tube on admission. 15 days later, due to the difficulty of re-inserting the nasogastric tube, endoscopy found a large number of coagulations in the esophagus, resulting in complete esophageal obstruction. We remove a small part of the foreign body with a net basket under gastroscope. After the operation, the nasogastric tube was placed in the middle of the esophagus again, which was perfused with 5% sodium bicarbonate and vinegar through the gastric tube. One week later, the esophagus was completely unobstructed by gastroscopy. A conclusion can be drawn that the precipitation and coagulation of TPF can lead to the whole esophageal obstruction. Endoscopic removal of foreign bodies, sodium bicarbonate and vinegar retention in the esophagus can treat the food obstruction caused by TPF.

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