Program Schedule

1672
Streptococcus pneumoniae Evades the Acute Inflammatory Response to Mucosal Colonization through Regulation of the Paracrine Lipid Mediator Platelet-Activating Factor

Session: Poster Abstract Session: Microbial and Host Factors
Saturday, October 11, 2014
Room: The Pennsylvania Convention Center: IDExpo Hall BC
Background:

Streptococcus pneumoniae (the pneumococcus) remains a leading cause of infectious mortality worldwide. Acquisition of the pneumococcus occurs at the nasopharyngeal mucosa and elicits a rapid influx of neutrophils (PMNs) to the nasal lumen. However, the pneumococcus efficiently eludes clearance by PMNs and persists in the nasopharynx weeks after the acute inflammatory response recedes, amplifying the risk of invasive disease. A growing number of studies implicate the secreted phospholipid platelet-activating factor (PAF) as an important local mediator of PMN recruitment and activation in response to mucosal infections. While the pneumococcus has been shown to secrete a cell wall-bound esterase, Pce, which efficiently hydrolyzes PAF in vitro, it remains unknown whether regulation of local PAF concentration influences pneumococcal survival during colonization. 

Methods:

We make use of atraumatic colonization of the murine nasopharynx to model carriage in the human upper respiratory tract.

Results:

We demonstrate that pneumococci lacking Pce (Pce-) elicit greater numbers of luminal PMNs with elevated expression of the phagocytic receptor CD11b compared to wild type (WT) bacteria. Despite unaltered sensitivity to PMN phagocytosis in vitro, Pce- bacteria exhibit a significant competitive survival defect during colonization which is completely abrogated upon systemic PMN depletion. Intranasal treatment with PAF receptor antagonists also abrogates the Pce- survival defect, indicating that local PAF signaling may mediate this PMN-dependent effect. In vitro, pre-incubation of PAF with WT (and not Pce-) pneumococcal lysates prior to PMN stimulation inhibits CD11b surface expression, suggesting Pce inhibits PAF-mediated PMN activation directly. Accordingly, restoration of neutrophil activation in vivo through intranasal administration of PAF or pro-inflammatory bacterial by-products suppresses the competitive advantage of wild type pneumococci over the Pce- mutant.

Conclusion:

Taken together, our findings suggest that pneumococcal Pce esterase contributes to innate immune evasion through hydrolysis of PAF, thereby actively inhibiting PMN phagocytic capacity in trans and promoting pneumococcal persistence during colonization.


Christopher Hergott, B.S., University of Pennsylvania, Philadelphia, PA

Disclosures:

C. Hergott, None

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