Cell-specific pattern recognition receptor signaling in antibacterial defense

In this study the relative roles of Toll-like receptor (TLR)2 and TLR4 were investigated independently and together. Moreover, we studied the role of hematopoietic compartment in anti-Klebsiella host defense. We infected TLR2, TLR4 singleand TLR2x4 double knock-out (KO) animals with different doses of Klebsiella pneumoniae. In addition, bone marrow chimeric mice were created and infected. TLR4 played a more prominent role in antibacterial defense than TLR2, considering that only TLR4 KO mice demonstrated enhanced bacterial growth in lungs and spleen 24 h after infection with 3x103 colony-forming units of Klebsiella compared with wild-type (WT) mice. In late stage infection or after exposure to a higher infectious dose, bacterial counts in lungs of TLR2 KO animals were elevated compared to WT mice and TLR2x4 KO animals were more susceptible to infection than TLR4 KO mice. TLR signaling on cells of hematopoietic origin is of primary importance in host defense against K. pneumoniae. These data suggest that 1) TLR4 drives the antibacterial host response after induction of pneumonia with relatively low Klebsiella doses; 2) TLR2 becomes involved at a later phase of the infection and/or upon exposure to higher bacterial burdens and (3) hematopoietic TLR2 and TLR 4 are important for an adequate host response during Klebsiella pneumonia.