Toll-like receptors are temporally involved in host defense

DS Weiss, B Raupach, K Takeda, S Akira… - The Journal of …, 2004 - journals.aai.org
DS Weiss, B Raupach, K Takeda, S Akira, A Zychlinsky
The Journal of Immunology, 2004journals.aai.org
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 …
Abstract
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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