The innate immune system and its relevance to neonatal sepsis.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Kenzel
Sybille
S
Zentrum für Kinderheilkunde und Jugendmedizin, Albert-Ludwigs Universität Freiburg, Freiburg, Germany.
Henneke
Philipp
P
D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007231:Infant, Newborn / Q000276:immunology*; D010586:Phagocytes; D011247:Pregnancy; D018805:Sepsis / Q000276:immunology* / Q000382:microbiology; D013290:Streptococcal Infections / Q000276:immunology* / Q000382:microbiology; D013292:Streptococcus agalactiae / Q000276:immunology*; D051193:Toll-Like Receptors / Q000276:immunology
D051193:Toll-Like Receptors