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2015 ; 10
(12
): e0145138
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English Wikipedia
Role of Nucleotide-Binding Oligomerization Domain-Containing (NOD) 2 in Host
Defense during Pneumococcal Pneumonia
#MMPMID26673231
Hommes TJ
; van Lieshout MH
; van 't Veer C
; Florquin S
; Bootsma HJ
; Hermans PW
; de Vos AF
; van der Poll T
PLoS One
2015[]; 10
(12
): e0145138
PMID26673231
show ga
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
(D39?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 D39?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.