| Sumario: |
It is not clear how the host initially recognizes and responds to infection by gram-negative pathogenic
Brucella spp. It was previously shown (D. S. Weiss, B. Raupach, K. Takeda, S. Akira, and A. Zychlinsky, J.
Immunol. 172:4463–4469, 2004) that the early macrophage response against gram-negative bacteria is medi ated by Toll-like receptor 4 (TLR4), which signals in response to lipopolysaccharide (LPS). Brucella, however,
has a noncanonical LPS which does not have potent immunostimulatory activity. We evaluated the kinetics of
TLR4 activation and the cytokine response in murine macrophages after Brucella infection. We found that
during infection of macrophages, Brucella avoids activation of TLR4 at 6 h but activates TLR4, TLR2, and
myeloid differentiation factor 88 (MyD88) at 24 h postinfection. Interestingly, even though its activation is
delayed, MyD88 is important for host defense against Brucella infection in vivo, since MyD88 / mice do not
clear the bacteria as efficiently as wild-type, TLR4 / , TLR2 / , or TLR4/TLR2 / mice.
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