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Neutrophil-Toxin Interactions Promote Antigen Delivery and Mucosal Clearance of Streptococcus pneumoniae¹

Kathryn A. Matthias^*, Aoife M. Roche^*, Alistair J. Standish^*, Mikhail Shchepetov^* and Jeffrey N. Weiser^2,*,

^* Department of Microbiology and Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by grants from the U.S. Public Health Service to J.N.W. (AI44231 and AI38446) and the Morphology Core of the Center for the Molecular Studies of Liver and Digestive Disease (Center Grant P30 DK50306).

² Address correspondence and reprint requests to Dr. Jeffrey N. Weiser, 402A Johnson Pavilion, Department of Microbiology and Pediatrics, University of Pennsylvania, Philadelphia, PA 19104. E-mail address: weiser{at}mail.med.upenn.edu

³ Abbreviations used in this paper: NALT, nasal-associated lymphoid tissue; IF, immunofluorescence; DAPI, 4',6-diamidino-2-phenylindole; Ply, purified pneumolysin; PdB, purified pneumolysin toxoid; LDH, lactate dehydrogenase; wt, wild type; UEA-1, Ulex europaeus agglutinin-1.