Role of endosomal toll-like receptors in immune sensing of Klebsiella pneumoniae

<i>Klebsiella pneumoniae</i> is the causative agent of a wide range of antibiotic-resistant infections, including nosocomial pneumonia and neonatal sepsis. We investigate here the mechanisms underlying innate immune recognition of this pathogen by focusing on the role of endosomal Toll-like receptors (TLRs), which sense prokaryotic nucleic acids, in comparison with TLR4, which recognizes the cell-wall lipopolysaccharide component. Lack of functional endosomal TLRs made mice more susceptible to pulmonary infection by <i>K. pneumoniae</i>, in association with reduced production of proinflammatory and chemotactic cytokines and reduced neutrophil recruitment to the lung. This phenotype was as severe as that of TLR4-deficient mice and only moderately milder than that of mice lacking the TLR adaptor MyD88. Notably, macrophages lacking at the same time TLR7, 9 and 13 were more defective than those lacking only TLR9 in their ability to produce proinflammatory cytokines, suggesting a role for the RNA sensing TLR7 and 13 receptors in <i>K. pneumoniae</i> recognition. Collectively, our results unveil the presence of an integrated system of DNA and RNA sensing TLRs that cooperates with TLR4 in immune detection and clearance of <i>K. pneumoniae</i>. These data may be useful to devise alternative therapeutic approaches aimed at stimulating responses against antibiotic-resistant <i>K. pneumoniae</i> strains.