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Publication : Toll-like receptors are temporally involved in host defense.

First Author  Weiss DS Year  2004
Journal  J Immunol Volume  172
Issue  7 Pages  4463-9
PubMed ID  15034062 Mgi Jnum  J:88721
Mgi Id  MGI:3036956 Doi  10.4049/jimmunol.172.7.4463
Citation  Weiss DS, et al. (2004) Toll-like receptors are temporally involved in host defense. J Immunol 172(7):4463-9
abstractText  Toll-like receptors (TLRs) are evolutionarily conserved proteins that recognize microbial molecules and initiate host defense. To investigate how TLRs work together to fight infections, we tested the role of TLRs in host defense against the Gram-negative bacterial pathogen, Salmonella. We show that TLR4 is critical for early cytokine production and killing of bacteria by murine macrophages. Interestingly, later on, TLR2, but not TLR4, is required for macrophage responses. Myeloid differentiation factor 88, an adaptor protein directly downstream of TLRs, is required for both early and late responses. TLR4, TLR2, and myeloid differentiation factor 88 are involved in murine host defense against Salmonella in vivo, which correlates with the defects in host defense observed in vitro. We propose a model where the sequential activation of TLRs tailors the immune response to different microbes.
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