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Infection and Immunity, October 2006, p. 5506-5512, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.00655-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Differential Role of Lipooligosaccharide of Neisseria meningitidis in Virulence and Inflammatory Response during Respiratory Infection in Mice

Maria Leticia Zarantonelli,1* Michel Huerre,2 Muhamed-Kheir Taha,1 and Jean-Michel Alonso1

Unité des Neisseria,1 Unité de Recherche et d'Expertise Histotechnologie et Pathologie, Institut Pasteur, 25-28 rue du Dr Roux, 75724 Paris Cedex 15, France2

Received 24 April 2006/ Returned for modification 7 June 2006/ Accepted 7 July 2006

Meningococcal lipooligosaccharide (LOS) induces a strong proinflammatory response in humans during meningococcal infection. We analyzed the role of LOS in the inflammatory response and virulence during the early infectious process in a mouse model of meningococcal respiratory challenge. An lpxA mutant strain (serogroup B) devoid of LOS (strain Z0204) could not persist in the lungs and did not invade the blood. The persistence in the lungs and invasion of the bloodstream by a rfaD mutant expressing truncated LOS with only lipid A and 3-deoxy-D-manno-2-octulosonic acid molecules (strain Z0401) was intermediate between those of the wild-type and Z0204 strains. Both LOS mutants induced acute pneumonia with the presence of infiltrating polymorphonuclear leukocytes in lungs. Although tumor necrosis factor alpha production was reduced in mice infected with the mutant of devoid LOS, both LOS mutants induced production of other proinflammatory cytokines, such as interleukin-1ß (IL-1ß), IL-6, and the murine IL-8 homolog KC. Together, these results suggest that meningococcal LOS plays a role during the early infectious and invasive process, and they further confirm that other, nonlipopolysaccharide components of Neisseria meningitidis may significantly contribute to the inflammatory reaction of the host.

* Corresponding author. Mailing address: Unité des Neisseria, Institut Pasteur, 25-28 rue du Dr Roux, 75724 Paris Cedex 15, France. Phone: 33 1 45 68 89 58. Fax: 33 1 41 60 30 34. E-mail: lzaranto{at}pasteur.fr.

Editor: J. N. Weiser

Infection and Immunity, October 2006, p. 5506-5512, Vol. 74, No. 10
0019-9567/06/$08.00+0     doi:10.1128/IAI.00655-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.





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