Article

An anti-infective peptide that selectively modulates the innate immune response

University of British Columbia - Vancouver, Vancouver, British Columbia, Canada
Nature Biotechnology (Impact Factor: 39.08). 05/2007; 25(4):465-72. DOI: 10.1038/nbt1288
Source: PubMed

ABSTRACT We show that an innate defense-regulator peptide (IDR-1) was protective in mouse models of infection with important Gram-positive and Gram-negative pathogens, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus and Salmonella enterica serovar Typhimurium. When given from 48 h before to 6 h after infection, the peptide was effective by both local and systemic administration. Because protection by IDR-1 was prevented by in vivo depletion of monocytes and macrophages, but not neutrophils or B- and T-lymphocytes, we conclude that monocytes and macrophages are key effector cells. IDR-1 was not directly antimicrobial: gene and protein expression analysis in human and mouse monocytes and macrophages indicated that IDR-1, acting through mitogen-activated protein kinase and other signaling pathways, enhanced the levels of monocyte chemokines while reducing pro-inflammatory cytokine responses. To our knowledge, an innate defense regulator that counters infection by selective modulation of innate immunity without obvious toxicities has not been reported previously.

Full-text

Available from: Neeloffer Mookherjee, Jun 03, 2015
1 Follower
 · 
280 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Ganoderma lucidum is a basidiomycete white rot fungus that has been used for medicinal purposes worldwide. Although information concerning its genome and transcriptome has recently been reported, relatively little information is available for G. lucidum at the proteomic level. In this study, protein fractions from G. lucidum at three developmental stages (16-day mycelia, and fruiting bodies at 60 and 90 days) were prepared and subjected to LC-MS/MS analysis. A search against the G. lucidum genome database identified 803 proteins. Among these proteins, 61 lignocellulose degrading proteins were detected, most of which (49 proteins) were found in the 90-day fruiting bodies. Fourteen TCA-cycle related proteins, 17 peptidases, two argonaute-like proteins, and two immunomodulatory proteins were also detected. A majority (470) of the 803 proteins had GO annotations and were classified into 36 GO terms, with "binding", "catalytic activity", and "hydrolase activity" having high percentages. Additionally, 357 out of the 803 proteins were assigned to at least one COG functional category and grouped into 22 COG classifications. Based on the results from the proteomic and sequence alignment analyses, a potentially new immunomodulatory protein (GL18769) was expressed and shown to have high immunomodulatory activity. In this study, proteomic and biochemical analyses of G. lucidum were performed for the first time, revealing that proteins from this fungus can play significant bioactive roles and providing a new foundation for the further functional investigations that this fungus merits.
    PLoS ONE 03/2015; 10(3):e0119439. DOI:10.1371/journal.pone.0119439 · 3.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Hypoxic-ischemic encephalopathy (HIE) is a clinical condition in the neonate, resulting from oxygen deprivation around the time of birth. HIE affects 1–5/1000 live births worldwide and is associated with the development of neurological deficits, including cerebral palsy, epilepsy, and cognitive disabilities. Even though the brain is considered as an immune-privileged site, it has innate and adaptive immune response and can produce complement (C) components and antimicrobial peptides (AMPs). Dysregulation of cerebral expression of AMPs and C can exacerbate or ameliorate the inflammatory response within the brain. Brain ischemia triggers a prolonged inflammatory response affecting the progression of injury and secondary energy failure and involves both innate and adaptive immune systems, including immune-competent and non-competent cells. Following injury to the central nervous system (CNS), including neonatal hypoxia-ischemia (HI), resident microglia, and astroglia are the main cells providing immune defense to the brain in a stimulus-dependent manner. They can express and secrete pro-inflammatory cytokines and therefore trigger prolonged inflammation, resulting in neurodegeneration. Microglial cells express and release a wide range of inflammation-associated molecules including several components of the complement system. Complement activation following neonatal HI injury has been reported to contribute to neurodegeneration. Astrocytes can significantly affect the immune response of the CNS under pathological conditions through production and release of pro-inflammatory cytokines and immunomodulatory AMPs. Astrocytes express β-defensins, which can chemoattract and promote maturation of dendritic cells (DC), and can also limit inflammation by controlling the viability of these same DC. This review will focus on the balance of complement components and AMPs within the CNS following neonatal HI injury and the effect of that balance on the subsequent brain damage.
    Frontiers in Immunology 02/2015; 6. DOI:10.3389/fimmu.2015.00056
  • Source
    6th Animal science Congress; 06/2014