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Surfactant Protein a Resists the Bactericidal Effects of Pulmonary

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Surfactant Protein a Resists the Bactericidal Effects of Pulmonary Bordetella pertussis Lipopolysaccharide Resists the Bactericidal Effects of Pulmonary Surfactant Protein A This information is current as Lyndsay M. Schaeffer, Francis X. McCormack, Huixing Wu of September 29, 2021. and Alison A. Weiss J Immunol 2004; 173:1959-1965; ; doi: 10.4049/jimmunol.173.3.1959 http://www.jimmunol.org/content/173/3/1959 Downloaded from References This article cites 45 articles, 19 of which you can access for free at: http://www.jimmunol.org/content/173/3/1959.full#ref-list-1 http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 29, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2004 by The American Association of Immunologists All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. The Journal of Immunology Bordetella pertussis Lipopolysaccharide Resists the Bactericidal Effects of Pulmonary Surfactant Protein A1 Lyndsay M. Schaeffer,* Francis X. McCormack,† Huixing Wu,† and Alison A. Weiss2* Surfactant protein A (SP-A) plays an important role in the innate immune defense of the respiratory tract. SP-A binds to lipid A of bacterial LPS, induces aggregation, destabilizes bacterial membranes, and promotes phagocytosis by neutrophils and macro- phages. In this study, SP-A interaction with wild-type and mutant LPS of Bordetella pertussis, the causative agent of whooping cough, was examined. B. pertussis LPS has a branched core structure with a nonrepeating trisaccharide, rather than a long-chain repeating O-Ag. SP-A did not bind, aggregate, nor permeabilize wild-type B. pertussis. LPS mutants lacking even one of the sugars in the terminal trisaccharide were bound and aggregated by SP-A. SP-A enhanced phagocytosis by human monocytes of LPS mutants that were able to bind SP-A, but not wild-type bacteria. SP-A enhanced phagocytosis by human neutrophils of LPS- mutant strains, but only in the absence of functional adenylate cyclase toxin, a B. pertussis toxin that has been shown to depress Downloaded from neutrophil activity. We conclude that the LPS of wild-type B. pertussis shields the bacteria from SP-A-mediated clearance, possibly by sterically limiting access to the lipid A region. The Journal of Immunology, 2004, 173: 1959–1965. urfactant protein A (SP-A)3 is one of four known protein ponent of LPS suggests a mechanism for interaction with bacterial components of the pulmonary surfactant. Previous studies membranes (10). have demonstrated that SP-AϪ/Ϫ (knockout) mice have The LPS of organisms such as E. coli consists of a lipid A S http://www.jimmunol.org/ normal baseline pulmonary function (1, 2); however, when chal- domain, a relatively conserved core oligosaccharide, and an O-side lenged with a variety of viruses, bacteria, and fungi, these animals chain of repeating sugars. Bordetella pertussis, the causative agent proved to be more susceptible to respiratory infections (3, 4). SP-A of human whooping cough, and several other Gram-negative re- is a member of the collectin (collagen-like lectin) family of pro- spiratory pathogens, such as Moraxella catarrhalis, Neisseria teins. Like other collectins, including mannose-binding protein and meningitides, and Haemophilus influenzae, have an abbreviated surfactant protein D, SP-A participates in recognition and clear- LPS structure (14). B. pertussis lacks O-side chain (Fig. 1), and ance of microorganisms (for reviews, see Refs. 5 and 6). The in its place has a nonrepeating trisaccharide consisting of ␣-N- shared structural features of collectins include a globular carbohy- acetylglucosamine, ␤-2-acetamido-3-acetamido-2,3-dideoxy-man- drate recognition domain (CRD) at the C terminus, an amphipathic nuronic acid, and ␤-l-2-acetamido-4-methylamino-fucose (15, 16). by guest on September 29, 2021 helical neck region, an extended collagen-like domain, and a disulfide Electrophoresis of B. pertussis LPS reveals two distinct bands, bonded N-terminal region. SP-A monomers fold as a triple helix referred to as bands A and B (16). The slower migrating band A is through their collagen-like domains to form trimers, and six trimers composed of full-length LPS containing lipid A, core oligosaccha- assemble into a bouquet of tulips structure, which resembles C1q, the ride, and the terminal trisaccharide. Band B migrates faster and is first component of complement (7). The crystal structure of the composed of lipid A and core oligosaccharide, but lacks the tri- C-terminal domains of SP-A has been reported recently (8). saccharide (16). The simple structure of the B. pertussis LPS and SP-A can bind to a variety of microorganisms, including Esch- the availability of LPS-mutant forms of B. pertussis provide a erichia coli and Pseudomonas aeruginosa (9–11), induce aggre- unique opportunity to study the molecular basis of the interaction gation (9, 10, 12), and promote phagocytosis (9, 11, 13). The struc- between LPS and SP-A. tural basis of these functions is not completely understood, but The sugars of the terminal trisaccharide of B. pertussis are syn- evidence that SP-A binds via its CRD region to the lipid A com- thesized and attached to the core by the enzymes encoded in the 12-gene wlb operon (17, 18). A number of mutations have been introduced into this operon, leading to the generation of mutant strains lacking one, two, or all three of the terminal sugars. WlbH Departments of *Molecular Genetics, Biochemistry, and Microbiology, and †Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of Cincin- lacks the terminal sugar (17, 18), MLT7 appears to lack the last nati, Cincinnati, OH 45267 two sugars (19), and WlbG and WlbL lack all three sugars (17, 18). Received for publication July 22, 2003. Accepted for publication May 24, 2004. Homology studies have suggested that WlbL fails to produce the The costs of publication of this article were defrayed in part by the payment of page first sugar in the trisaccharide, while WlbG retains the ability to charges. This article must therefore be hereby marked advertisement in accordance produce this sugar, but fails to transfer it to the surface of the with 18 U.S.C. Section 1734 solely to indicate this fact. bacterial cell (18). 1 This work was supported by National Institutes of Health Grants RO1 AI45715 (to Allen et al. (20) have identified and mutated the waaF gene of A.A.W.) and HL61612 (to F.X.M.). B. pertussis. This gene is responsible for the addition of a heptose 2 Address correspondence and reprint requests to Dr. Alison A. Weiss, Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, 231 molecule at an early step in the synthesis of the core oligosaccha- Albert Sabin Way, ML 0524, Cincinnati, OH 45267-0524. E-mail address: ride (20). Mutation of this gene results in a truncated LPS molecule [email protected] with only lipid A, a single ketodeoxyoctulosonic acid (Kdo) res- 3 Abbreviations used in this paper: SP-A, surfactant protein A; BG, Bordet-Gengou; idue, and the first heptose residue of the core oligosaccharide (20). CRD, carbohydrate recognition domain; FHA, filamentous hemagglutinin; H-H, HBSS buffered with 10 mM HEPES; Kdo, ketodeoxyoctulosonic; MOI, multiplicity The LPS from WaaF mutants is smaller than band B LPS and fails of infection; SS, Stainer-Scholte; SS-BG, SS broth overlaid on BG agar. to react with mAbs against band B. Copyright © 2004 by The American Association of Immunologists, Inc. 0022-1767/04/$02.00 1960 B. pertussis LPS AND SP-A FIGURE 1. Schematic of the LPS of wild-type B. pertussis and LPS mutants. B. pertussis LPS is comprised of lipid A and core oligosaccharide. However, instead of a long, repeating O-side chain, B. pertussis LPS terminates in a simple trisaccharide composed of ␣-N-acetylglucosamine, ␤-2- acetamido-3-acetamido-2,3-dideoxy-mannuronic acid, and ␤-l-2-acetamido-4-methylamino-fucose. The structure of full-length band A LPS (A) and the truncated band B LPS (lacking the terminal trisaccharide) (B) are indicated on the right. The WaaF mutant has an abbreviated core structure consisting of Kdo and a single heptose residue. A Bvg mutant, BP347, fails to efficiently attach the trisaccharide and has been reported to express mixed (band A and B) LPS (19). Using wild-type, Wlb, and WaaF mutant strains of B. pertussis, gen, Carlsbad, CA). This plasmid was digested with HindIII and a 3-kb we have examined the LPS structural elements required for SP-A HindIII fragment from pUW2138, encoding gentamicin resistance, and the to bind, aggregate, opsonize, and kill B. pertussis. OriT region (to allow for mobilization from E. coli into B. pertussis), or gent/ OriT, was inserted to generate plasmid pLMS023 (Fig. 2). LMS023 was mo- bilized into B. pertussis by triparental mating, as previously described (37). A Materials and Methods kanamycin- and gentamicin-resistant colony was selected and screened for loss Downloaded from Bacterial strains and growth conditions of band A LPS by Western blot using a mAb to band A LPS, G10F8C3 (33). Plasmids and bacterial strains used in this study are described in Table I. Mutation of the adenylate cyclase toxin gene B. pertussis strains containing a plasmid encoding GFP introduced by elec- troporation (22) were used, except where indicated.
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