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Infect. Immun. doi:10.1128/IAI.01716-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Lipooligosaccharides containing phosphorylcholine delay pulmonary clearance of nontypeable Haemophilus influenzae

Departments of Microbiology, and Pathology, Wake Forest University School of Medicine

^* To whom correspondence should be addressed. Email: wswords{at}wfubmc.edu.

	Abstract

Nontypeable Haemophilus influenzae (NTHi ) causes pulmonary infections in patients with chronic obstructive pulmonary disease and other mucociliary clearance defects. Like many bacteria inhabiting mucosal surfaces, NTHi produces lipooligosaccharide (LOS) endotoxins that lack O side-chain. Persistent NTHi populations express a discrete subset of LOS glycoforms including those containing phosphorylcholine (PCho). In this study, we compared two NTHi strains with isogenic mutants lacking PCho for clearance from mice following pulmonary infection. Consistent with data from other model systems, populations of NTHi 2019 and 86-028NP recovered from mouse lung contained an increased proportion of PCho+ variants as compared to the inocula. PCho- mutants were more rapidly cleared. Serial passage of NTHi increased both PCho content and bacterial resistance to clearance, and no such increases were observed for PCho- mutants. Increased PCho content was also observed in NTHi populations within endotoxin-nonresponsive C3H/HeJ and TLR4 -/- mice, albeit at later times post-infection. Changes in bacterial subpopulations and clearance were unaffected in TLR2 -/- mice as compared to the parental mouse strain. Clearance of PCho- mutants occurred at earlier time points in both strain backgrounds and in all types of mice. Comparison of bacterial populations in lung tissue cryosections by immunofluorescent staining showed sparse bacteria within the air spaces of C57BL/6 mice, and large bacterial aggregates within the lungs of MyD88 -/- mice. These results indicate that PCho promotes bacterial resistance to pulmonary clearance early in infection, in a manner that is at least partially independent of the Toll-like receptor 4 pathway.