Neutrophil-Toxin Interactions Promote Antigen Delivery and Mucosal Clearance of Streptococcus pneumoniae

Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.
The Journal of Immunology (Impact Factor: 4.92). 06/2008; 180(9):6246-54. DOI: 10.4049/jimmunol.180.9.6246
Source: PubMed


Delivery of Ag to inductive sites, such as nasal-associated lymphoid tissue (NALT) or GALT, is thought to promote mucosal immunity. Host and microbial factors that contribute to this process were investigated during model murine airway colonization by the pathogen Streptococcus pneumoniae. Colonization led to the deposition of released bacterial capsular Ag in the NALT in a manner consistent with trafficking through M cells. This Ag was derived from processing of bacteria in the lumen of the paranasal spaces rather than through invasion or sampling of intact bacteria. Neutrophils, which are recruited to the paranasal spaces where they associate with and may degrade bacteria, were required for efficient Ag delivery. Maximal Ag delivery to the NALT also required expression of the bacterial toxin pneumolysin. Pneumolysin and pneumolysin-expressing bacteria lysed neutrophils through pore formation in vitro. Accordingly, a pneumolysin-dependent loss of neutrophils, which correlated with the increased release of bacterial products, was observed in vivo. Thus, delivery of Ag to the NALT was enhanced by neutrophil-mediated generation of bacterial products together with bacterial-induced lysis of neutrophils. The impaired Ag delivery of pneumolysin-deficient bacteria was associated with diminished clearance from the mucosal surface. This study demonstrates how microbial-host interactions affect Ag delivery and the effectiveness of mucosal immunity.

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    • "This phenomenon associated with DT treatment has been previously described by Tittel et al. (2012). As neutrophils are the most important innate immune cells for early defense against S. pneumoniae (Matthias et al., 2008; Standish and Weiser, 2009), it can be hypothesized that a higher amount of neutrophils present in the lungs of DT-treated mice previous to bacterial challenge can be responsible for the lower bacterial burdens observed in these animals at later time points. However, the fact that the amount of bacteria in the lungs at 24 h after intranasal challenge is comparable in PBS- and DT-treated mice gives clear indication that the greater amount of neutrophils in the lungs of the later mice is not responsible for the superior resistance of these animals. "
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    • "Pneumococcal infections are controlled by host neutrophils, which kill this pathogen via opsonophagocytosis (OPH), a process that requires opsonization of bacteria by the complement system (Dalia et al., 2010; Lysenko et al., 2007; Matthias et al., 2008). "
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