PT  - JOURNAL ARTICLE
AU  - C.W. Wieland
AU  - M.H.P. van Lieshout
AU  - A.J. Hoogendijk
AU  - T. van der Poll
TI  - Host defense during <em>Klebsiella</em> pneumonia relies on hematopoietic expressed TLR4 and TLR2
AID  - 10.1183/09031936.00076510
DP  - 2010 Jan 01
TA  - European Respiratory Journal
PG  - erj00765-2010
4099  - http://erj.ersjournals.com/content/early/2010/07/22/09031936.00076510.short
4100  - http://erj.ersjournals.com/content/early/2010/07/22/09031936.00076510.full
AB  - With this study the relative roles of Toll-like receptor (TLR)2 and -4 were investigated independently and together. Moreover, we studied the role of hematopoietic compartment in anti-Klebsiella host defense.We infected TLR2, TLR4 and TLR2x4 double KO animals with different doses of K. 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 3×103 Klebsiella compared to 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 TLR2×4 KO animals were more susceptible to infection than TLR4 KO mice. TLR signaling on cells from 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 TLR2/4 are important for an adequate host response during Klebsiella pneumonia.