Differential Effect of TLR2 and TLR4 on the Immune Response after Immunization with a Vaccine against Neisseria meningitidis or Bordetella pertussis

Floris Fransen,Rachel M Stenger,Harry H Van Dijken,Jos P M Van Putten,Betsy Kuipers,Claire J P Boog,Martien C M Poelen,Peter Van Der Ley,Cécile A C M Van Els,Jacques Zimmer

doi:10.1371/journal.pone.0015692

Floris Fransen, Rachel M Stenger + Show 8 more

Open Access

https://doi.org/10.1371/journal.pone.0015692

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Journal: PloS one	Publication Date: Dec 23, 2010
Citations: 67	License type: CC BY 4.0

Affiliation: Utrecht University

Abstract

Neisseria meningitidis and Bordetella pertussis are Gram-negative bacterial pathogens that can cause serious diseases in humans. N. meningitidis outer membrane vesicle (OMV) vaccines and whole cell pertussis vaccines have been successfully used in humans to control infections with these pathogens. The mechanisms behind their effectiveness are poorly defined. Here we investigated the role of Toll-like receptor (TLR) 2 and TLR4 in the induction of immune responses in mice after immunization with these vaccines. Innate and adaptive immune responses were compared between wild type mice and mice deficient in TLR2, TLR4, or TRIF. TRIF-deficient and TLR4-deficient mice showed impaired immunity after immunization. In contrast, immune responses were not lower in TLR2−/− mice but tended even to be higher after immunization. Together our data demonstrate that TLR4 activation contributes to the immunogenicity of the N. meningitidis OMV vaccine and the whole cell pertussis vaccine, but that TLR2 activation is not required.

Highlights

The innate immune system senses microbes through a number of receptors present on innate immune cells that can recognize a wide variety of microbial structures [1]
We demonstrate that TLR4 signalling by LPS contributes to generation of adaptive immune responses after immunization with N. meningitidis outer membrane vesicle (OMV) or whole cell pertussis vaccine, while TLR2 activation was not required
TLR22/2 mice overall showed higher rather than lower responses compared to C57BL/6 mice after immunization with the N. meningitidis and B. pertussis vaccines

Summary

Introduction

The innate immune system senses microbes through a number of receptors present on innate immune cells that can recognize a wide variety of microbial structures [1]. This group of receptors is often referred to as pattern recognition receptors (PRRs). TLR4 is the only TLR which utilizes both MyD88 and TRIF [4] Activation of these proteins eventually leads to induction of proinflammatory cytokines and type I interferon, respectively. Activation of TLR7/8 and TLR9 leads to the induction of type I interferon, but in a MyD88-dependent manner [1]

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