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Current Opinion in Infectious Diseases:
doi: 10.1097/01.qco.0000224821.27482.bd
Paediatric and neonatal infections

The innate immune system and its relevance to neonatal sepsis

Kenzel, Sybille; Henneke, Philipp

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Abstract

Purpose of review: The advent of human Toll-like receptors has revolutionized our understanding of innate immunity. This review summarizes recent discoveries about the role of Toll-like receptors and innate immunity in neonatal sepsis with a particular emphasis on the paradigmatic organism S. agalactiae.

Recent findings: S. agalactiae stimulates phagocytes to excessive formation of inflammatory cytokines such as tumor necrosis factor, and Toll-like receptors are essential for this response both in vivo and in vitro. On the molecular level, distinct signaling pathways are engaged by released S. agalactiae toxins such as lipoteichoic acid (Toll-like receptor-2 dependent) and cell-bound toxins (Toll-like receptor-2 independent). In contrast, complement receptors and Fc receptors, but not Toll-like receptors, are directly involved in phagocytosis and therefore elimination of S. agalactiae. Notably, neonatal phagocytes potently activate cytokines in response to S. agalactiae but are deficient in S. agalactiae uptake and killing. Interference with the Toll-like receptor-dependent mitogen activated protein kinase cJun N-terminal Kinase improves outcome in a neonatal model of S. agalactiae sepsis by inhibiting cytokine formation but preserving clearance of S. agalactiae.

Summary: Recent progress in the understanding of S. agalactiae recognition and phagocytic signaling in neonatal sepsis suggests intermediates in the Toll-like receptor pathways as valuable targets for adjunctive sepsis therapy.

© 2006 Lippincott Williams & Wilkins, Inc.

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