Journal Article

The Role of Toll-Like Receptors in the Regulation of Neutrophil Migration, Activation, and Apoptosis

Ian Sabroe, Steven K. Dower and Moira K. B. Whyte

in Clinical Infectious Diseases

Published on behalf of Infectious Diseases Society of America

Volume 41, issue Supplement_7, pages S421-S426
Published in print November 2005 | ISSN: 1058-4838
Published online November 2005 | e-ISSN: 1537-6591 | DOI: http://dx.doi.org/10.1086/431992
The Role of Toll-Like Receptors in the Regulation of Neutrophil Migration, Activation, and Apoptosis

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Toll-like receptors (TLRs) playan essential role inthe detection of invading pathogens and in theinduction of host antimicrobial defenses. TLR4, the major endotoxin receptor, and TLR2, with agonists derived principally from gram-positive organisms, are likely to be important in the pathogenesis of sepsis. Both TLR2 and TLR4 agonists regulate important neutrophil functions, including adhesion, generation of reactive oxygen species, and release of chemokines, and activate major proinflammatory signaling pathways, including the nuclear factor—κB path way. TLR stimulation produces on lya modest direct inhibition of neutrophil apoptosis, although this signal is great lyamplified by the presence of monocytes, suggesting that regulation of the lifespan of neutrophils by TLR agonists may beprincipally mediated by responses of other end otoxin-responsive cells. We suggest that activation of neutrophils by TLR sis highly regulated, permitting acute neutrophil antimicrobial responses to TLR activation while providing a “brake” on inflammation by requiring the presence of mononuclear cells to significantly extend neutronphil survival.

Journal Article.  4295 words.  Illustrated.

Subjects: Infectious Diseases ; Immunology ; Public Health and Epidemiology ; Microbiology

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