Mucosal Clearance of Capsule-Expressing Bacteria Requires Both TLR and Nucleotide-Binding Oligomerization Domain 1 Signaling

Abstract

Expression of capsular polysaccharide by bacterial pathogens is associated with increased resistance to host clearance mechanisms, in particular by evading opsonization and uptake by professional phagocytes. The potential for rapid progression of disease caused by encapsulated bacteria points to the importance of innate immunity at the mucosal surface where infection is initiated. Using a murine model of nasopharyngeal colonization, host immune components that contribute to the mucosal clearance of capsule-expressing bacteria were investigated. Clearance of encapsulated Haemophilus influenzae (Hi) required both TLR and nucleotide-binding oligomerization domain (NOD) signaling pathways, whereas individual deficiencies in each of these signaling cascades did not affect clearance of nonencapsulated strains. Moreover, clearance of Hi-expressing capsular polysaccharide required the recruitment of neutrophils to the site of infection, and ex vivo phagocytic bacterial killing required expression of the NOD1 signaling pathway. Conversely, redundancies within these innate immune pathways of non-neutrophil cells were sufficient to promote mucosal clearance of nonencapsulated Hi. Our findings reveal a role for NOD1 in protection from encapsulated pathogens. In addition, this study provides an example of a microbial virulence determinant that alters the requirements for host signaling to provide effective protection.

Morphine Inhibits Murine Dendritic Cell IL-23 Production by Modulating Toll-like Receptor 2 and Nod2 Signaling

“…Nod1 and Nod2 recognize the bacterial peptidoglycan components ␥-D-glutamyl-mesodiaminopimelic acid and muramyl dipeptide (MDP), respectively (12). Nod2 activation seems to play an important role in host cell activation by internalized pneumococci (13). Findings from our lab indicate that IL-23 is produced by DCs and macrophages within a few hours after exposure to S. pneumoniae.…”

Bacterial exploitation of phosphorylcholine mimicry suppresses inflammation to promote airway infection

“…Akin to results observed with Δpce pneumococci, neutropenia rescued ΔglpQ survival such that it resembled that of WT H. influenzae ( Figure 7F). ΔglpQ survival was also rescued as it displays ChoP on surface-exposed lipooligosaccharide chains (28), remains an important cause of respiratory disease worldwide (59,60), and could be investigated using a murine model of upper respiratory tract infection (61). No direct homologs for pneumococcal Pce were apparent in H. influenzae by sequence analysis.…”

Innate Immunity of Airway Epithelium and COPD

“…These two NODs are also expressed in airway epithelium and are induced by bacterial stimuli (Bogefors et al, 2010;Mayer et al, 2007;Opitz et al, 2004;Travassos et al, 2005). NOD1 and NOD2 contribute to innate immune responses to different bacteria including Pseudomonas aeruginosa, Chlamydia pneumonia, Haemophilus influenza and L. pneumophila both in vivo and in vitro (Clarke et al, 2010;Frutuoso et al, 2010;Shimada et al, 2009;Zola et al, 2008).…”