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Open AccessJournal ArticleDOI

Phagocytosis and the Inflammatory Response

TLDR
After generating a panel of 150 monoclonal antibodies that recognizes proteins recruited to the phagosome, analysis of novel phagocytic proteins was prioritized by focusing on those that behave differently during the internalization of virulent and avirulent bacteria.
Abstract
Macrophages are a cornerstone of the innate immune system. They detect infectious organisms via a plethora of receptors, phagocytose them, and orchestrate an appropriate host response. Phagocytosis is extraordinarily complex: numerous receptors stimulate particle internalization, the cytoskeletal elements mediating internalization differ by receptor system and the nature of the pathogen being internalized, and the outcome can differ by bacterium. After generating a panel of 150 monoclonal antibodies that recognizes proteins recruited to the phagosome, analysis of novel phagocytic proteins was prioritized by focusing on those that behave differently during the internalization of virulent and avirulent bacteria. Several novel proteins that have roles in membrane extension were characterized. Although the inflammatory pathways leading to appropriate host response are reasonably well defined, it is not clear how macrophages define the threat precisely. Recent work indicates that Toll-like receptors play a key role in reading a bar code on invading microorganisms and in eliciting a specific immune response. The mechanisms and coupling to the phagocytic response are discussed.

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Journal ArticleDOI

The interface between innate and adaptive immunity.

TL;DR: This focus analyzes some of the ways the innate immune system influences adaptive immune responses and discusses the main principles and themes that govern this intricate relationship.
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Patterns of pathogenesis: discrimination of pathogenic and nonpathogenic microbes by the innate immune system.

TL;DR: The idea that the immune system responds to PAMPs in the context of additional signals that derive from common "patterns of pathogenesis" employed by pathogens to infect, multiply within, and spread among their hosts is explored.
Journal ArticleDOI

LPS receptor (CD14): a receptor for phagocytosis of Alzheimer’s amyloid peptide

TL;DR: A direct role of CD14 in Abeta(42) phagocytosis is demonstrated, and a pronounced CD14 immunoreactivity on parenchymal microglia spatially correlated to characteristic Alzheimer's disease lesion sites in brain sections of Alzheimer’s disease patients but not inbrain sections of control subjects are detected.
Journal ArticleDOI

Defective macrophage phagocytosis of bacteria in COPD

TL;DR: COPD macrophage innate responses are suppressed and may lead to bacterial colonisation and increased exacerbation frequency, which suggests that bacterial infection in COPD could be due to reduced pathogen removal.
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Biodistribution and toxicity of intravenously administered silica nanoparticles in mice.

TL;DR: The results indicated that SiNPs accumulate mainly in lungs, liver and spleen and are retained for over 30 days in the tissues because of the endocytosis by macrophages, and could potentially cause liver injury when intravenously injected.
References
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Journal ArticleDOI

Defective LPS Signaling in C3H/HeJ and C57BL/10ScCr Mice: Mutations in Tlr4 Gene

TL;DR: The mammalian Tlr4 protein has been adapted primarily to subserve the recognition of LPS and presumably transduces the LPS signal across the plasma membrane.
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Toll-like receptors: critical proteins linking innate and acquired immunity.

TL;DR: Evidence is accumulating that the signaling pathways associated with each TLR are not identical and may, therefore, result in different biological responses.
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Toll-like receptors and innate immunity

TL;DR: This work has shown that activation of inflammatory and antimicrobial innate immune responses through recognition of Toll-like receptors expressed on dendritic cells triggers functional maturation of dendrites and leads to initiation of antigen-specific adaptive immune responses.
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Toll-like receptors in the induction of the innate immune response

TL;DR: A group of proteins that comprise the Toll or Toll-like family of receptors perform this role in vertebrate and invertebrate organisms and it is therefore not surprising that studies of the mechanism by which they act has revealed new and important insights into host defence.