Publications by authors named "David Goucher"

Article Synopsis
  • Viral encephalitides pose a serious threat to neonates due to inflammation-induced damage to the central nervous system (CNS), prompting this study to investigate proinflammatory cytokines' roles in managing viral replication and harmful immune responses.
  • Neonatal mice infected with the arenavirus Tacaribe (TCRV) exhibited a severe form of meningoencephalitis, but neutralizing TNF-alpha led to reduced inflammation and improved survival outcomes, despite not clearing the virus.
  • Combining anti-TNF-alpha antibodies with innate immune activators resulted in complete viral clearance and 100% survival, marking a significant advancement in therapeutic strategies for deadly viral infections affecting the nervous system.
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The innate immune system is key to limiting the early spread of most pathogens and directing the development of Ag-specific immunity. Recently, a number of synthetic molecules that activate the innate immune system by stimulating TLRs have been identified. Among them, synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs (CpG ODNs) were shown to activate TLR9-bearing B cells, macrophages, and dendritic cells to induce a strong proinflammatory milieu and a type 1-biased immune response that protects mice from a variety of parasitic, bacterial, and viral infections.

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Activation of peripheral CD4+ T cells resulted in augmented fusion with X4 human immunodeficiency virus type 1 (HIV-1) envelope-expressing cells without parallel increases in the surface expression of CD4 or CXC chemokine receptor 4 (CXCR4). Our study used biochemical methods and biological assays to correlate the increased fusion potential of activated T cells with changes in CXCR4 isoforms and CD4-CXCR4 association. Western blot analyses of CXCR4, precipitated from resting T cells, identified several CXCR4 species with molecular weights of 47, 50, 62, and 98 kDa.

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