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Streptococcus (S . ) pneumoniae  is the most common causative pathogen in community-acquired pneumonia. Nucleotide-binding oligomerization domain-containing (NOD) 2 is a pattern recognition receptor located in the cytosol of myeloid cells that is able to detect peptidoglycan fragments of  S .  pneumoniae . We here aimed to investigate the role of NOD2 in the host response during pneumococcal pneumonia. Phagocytosis of  S .  pneumoniae  was studied in NOD2 deficient ( Nod2    -/-  ) and wild-type (Wt) alveolar macrophages and neutrophils  in vitro . In subsequent  in vivo  experiments  Nod2    -/-   and Wt mice were inoculated with serotype 2  S .  pneumoniae  (D39), an isogenic capsule locus deletion mutant (D39Δ cps ) or serotype 3  S .  pneumoniae  (6303) via the airways, and bacterial growth and dissemination and the lung inflammatory response were evaluated.  Nod2    -/-   alveolar macrophages and blood neutrophils displayed a reduced capacity to internalize pneumococci  in vitro . During pneumonia caused by  S .  pneumoniae  D39  Nod2    -/-   mice were indistinguishable from Wt mice with regard to bacterial loads in lungs and distant organs, lung pathology and neutrophil recruitment. While  Nod2    -/-   and Wt mice also had similar bacterial loads after infection with the more virulent  S .  pneumoniae  6303 strain,  Nod2    -/-   mice displayed a reduced bacterial clearance of the normally avirulent unencapsulated D39Δ cps  strain. These results suggest that NOD2 does not contribute to host defense during pneumococcal pneumonia and that the pneumococcal capsule impairs recognition of  S .  pneumoniae  by NOD2.

Role of Nucleotide-Binding Oligomerization Domain-Containing (NOD) 2 in Host Defense during Pneumococcal Pneumonia