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Infection and Immunity, June 2006, p. 3538-3546, Vol. 74, No. 6
0019-9567/06/$08.00+0     doi:10.1128/IAI.00128-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

MyD88-Dependent Signaling Affects the Development of Meningococcal Sepsis by Nonlipooligosaccharide Ligands

Laura Plant,^1,2* Hong Wan,¹ and Ann-Beth Jonsson¹

Department of Medical Biochemistry and Microbiology, Biomedical Centrum, Uppsala University, 751 23 Uppsala, Sweden,¹ Smittskyddsinstitutet, Swedish Institute for Infectious Disease Control, Karolinska Institutet, Nobelsväg 18, 171 77 Solna, Sweden²

Received 25 January 2006/ Returned for modification 9 March 2006/ Accepted 24 March 2006

The Toll-like receptors (TLRs) and the adaptor myeloid differentiation factor 88 (MyD88) are important in the innate immune defenses of the host to microbial infections. Meningococcal ligands signaling via TLRs control inflammatory responses, and stimulation can result in fulminant meningococcal sepsis. In this study, we show that the responses to nonlipooligosaccharide (non-LOS) ligands of meningococci are MyD88 dependent. An isogenic LOS-deficient mutant of the serogroup C meningococcal strain FAM20 caused fatal disease in wild type C57BL/6 mice that was not observed in MyD88^–/– mice. Fatality correlated with high proinflammatory cytokine and C5a levels in serum, high neutrophil numbers in blood, and increased bacteremia at 24 h postinfection in the wild-type mice. Infection with the parent strain FAM20 resulted in fatality in 100% of the wild-type mice and 50% of the MyD88^–/– mice. We conclude that both LOS and another neisserial ligand cause meningococcal sepsis in an in vivo mouse model and confirm that meningococcal LOS can act via both the MyD88- dependent and -independent pathways, while the non-LOS meningococcal ligand(s) acts only via the MyD88-dependent pathway.

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* Corresponding author. Mailing address: Smittskyddsinstitutet, Swedish Institute for Infectious Disease Control, Karolinska Institutet, Nobelsväg 18, 171 77 Solna, Sweden. Phone: 46 8457 24 32. Fax: 46 830 25 66. E-mail: Laura.Plant{at}smi.ki.se.

Editor: J. N. Weiser

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Infection and Immunity, June 2006, p. 3538-3546, Vol. 74, No. 6
0019-9567/06/$08.00+0     doi:10.1128/IAI.00128-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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