Identification of Adjuvantic Activity of Amphotericin B in a Novel, Multiplexed, Poly-TLR/NLR High-Throughput Screen

Autor: Karishma K. Khetani, Lauren M. Fox, Giuseppe Caruso, Alex C. D. Salyer, Sunil A. David, Subbalakshmi S. Malladi
Jazyk: angličtina
Rok vydání: 2016
Předmět:
0301 basic medicine
Nystatin
Physiology
medicine.medical_treatment
Monophosphoryl Lipid A
lcsh:Medicine
Pharmacology
Immune Receptors
Biochemistry
Immunologic Adjuvants
Cell Signaling
Microbial Physiology
Immune Physiology
NOD1
Medicine and Health Sciences
Public and Occupational Health
Membrane Receptor Signaling
Bacterial Physiology
Receptors
Immunologic
lcsh:Science
Toll-like Receptors
Vaccines
Innate Immune System
Multidisciplinary
Immune System Proteins
Effector
Antimicrobials
Drugs
Immune Receptor Signaling
Vaccination and Immunization
Cytokines
Adjuvant
Research Article
Signal Transduction
Immunology
Mycology
Biology
Microbiology
Cell Line
03 medical and health sciences
Adjuvants
Immunologic
Microbial Control
Amphotericin B
Vaccine Development
medicine
Humans
Antifungals
Innate immune system
lcsh:R
Biology and Life Sciences
Proteins
Bacteriology
Cell Biology
TLR8
Molecular Development
TLR2
030104 developmental biology
Immune System
TLR3
lcsh:Q
Preventive Medicine
Flagellin
Developmental Biology
Zdroj: PLoS ONE, Vol 11, Iss 2, p e0149848 (2016)
PLoS ONE
ISSN: 1932-6203
Popis: Small-molecule agonists have been identified for TLR7, TLR8, TLR4 and TLR2 thus far, and chemotypes other than those of canonical ligands are yet to be explored for a number of innate immune receptors. The discovery of novel immunostimulatory molecules would enhance the repertoire of tools available for interrogating innate immune effector mechanisms, and provide additional venues for vaccine adjuvant development. A multiplexed, reporter gene-based high-throughput assay capable of detecting agonists of TLR2, TLR3, TLR4, TLR5, TLR7, TLR8, TLR9, NOD1 and NOD2 was utilized in screening 123,943 compounds, in which amphotericin B (AmpB) and nystatin were identified as prominent hits. The polyene antifungal agents act as TLR2- and TLR4-agonists. The TLR4-stimulatory activity of AmpB was similar to that of monophosphoryl lipid A, suggestive of TRIF-biased signaling. The adjuvantic activity of AmpB, at a dose of 100 micrograms, was comparable to several other candidate adjuvants in rabbit models of immunization. These results point to its potential applicability as a safe and effective adjuvant for human vaccines.
Databáze: OpenAIRE
Externí odkaz: