Additional evidence implicating a role for TLR signaling in the development of pulmonary inflammation may be found in studies examining the development of pulmonary inflammation in human patients with TLR polymorphisms. For instance, polymorphisms in TLR4 (Ala299Gly and Thr399Ile), which are known to lead to hyporesponsiveness to LPS (187), lead to a marked resistance to infection with Legionella pneumophila (188) . These TLR4 mutations have been correlated with the development of severe RSV infection in infants (120) . An inactivating polymorphism in TLR5 (TLR5392STOP) that encodes a stop codon in the ligand binding domain of TLR5 is associated with an increased susceptibility to infection with Legionella pneumophila causing Legionnaire's disease (188) . Taken in aggregate, the results of these in vitro and in vivo studies provide evidence for a role for TLR signaling in the pathogenesis of pulmonary inflammation. Additional studies are required utilizing pulmonary-specific TLR deletions to further delineate the relative contributions of pulmonary epithelial cell versus infiltrating leukocytes in the development of mucosal inflammation in the lung.