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Activation of human dendritic cells by the PorA protein of Neisseria meningitidis

Activation of human dendritic cells by the PorA protein of Neisseria meningitidis
Activation of human dendritic cells by the PorA protein of Neisseria meningitidis
The major porin proteins present in the outer membrane of Neisseria meningitidis, the causative agent of life-threatening meningitis and septicaemia, are believed to have potent immunostimulatory effects. In this study, the interactions between human monocyte-derived dendritic cells (mo-DC) and the PorA porin were investigated, in order to reveal the role of this protein in promoting innate and adaptive immune responses. Recombinant (r)PorA induced mo-DC maturation, as reflected by reduced receptor-mediated endocytosis, increased production of the chemokines IL-8, RANTES, MIP-1? and MIP-1? and augmented expression of the surface markers CD40, CD54, CD80, CD86 and major histocompatibility complex class II molecules. However, rPorA induced either low level or no significant secretion of pro-inflammatory cytokines from mo-DC. The protein potently augmented the capacity of mo-DC to activate both allogeneic CD4+ memory T-cells and CD4+RA+ naïve T-cells. In addition, rPorA appeared to inhibit the production of IL-12p70 that follows from the interaction between CD40 on the mo-DC and CD40-ligand on T-cells, thereby directing T-cell differentiation towards a Th2 type response. These data demonstrate that PorA is involved in DC activation and in influencing the nature of the T-helper immune response, which are important properties for generating antibody responses required for protective immunity against meningococci and for determining the immuno-adjuvant effects of this protein.
1462-5814
651-662
Al-Bader, Tamara
a59b058a-c9a1-4a9b-ba54-ba45643fb470
Jolley, Keith A.
4ae51ae9-7a80-4ce0-a61c-1828b602d2ac
Humphries, Holly E.
dfbfbf86-71b7-4a11-8192-0afd0eb817a6
Holloway, Judith
f22f45f3-6fc8-4a4c-bc6c-24add507037c
Heckels, John E.
fcfcfafe-5ca8-4728-9c5e-cb67f9af7e31
Semper, Amanda E.
7271f3d0-051a-444d-a75f-e1d374a93bc8
Friedmann, Peter S.
d50bac23-f3ec-4493-8fa0-fa126cbeba88
Christodoulides, Myron
eba99148-620c-452a-a334-c1a52ba94078
Al-Bader, Tamara
a59b058a-c9a1-4a9b-ba54-ba45643fb470
Jolley, Keith A.
4ae51ae9-7a80-4ce0-a61c-1828b602d2ac
Humphries, Holly E.
dfbfbf86-71b7-4a11-8192-0afd0eb817a6
Holloway, Judith
f22f45f3-6fc8-4a4c-bc6c-24add507037c
Heckels, John E.
fcfcfafe-5ca8-4728-9c5e-cb67f9af7e31
Semper, Amanda E.
7271f3d0-051a-444d-a75f-e1d374a93bc8
Friedmann, Peter S.
d50bac23-f3ec-4493-8fa0-fa126cbeba88
Christodoulides, Myron
eba99148-620c-452a-a334-c1a52ba94078

Al-Bader, Tamara, Jolley, Keith A., Humphries, Holly E., Holloway, Judith, Heckels, John E., Semper, Amanda E., Friedmann, Peter S. and Christodoulides, Myron (2004) Activation of human dendritic cells by the PorA protein of Neisseria meningitidis. Cellular Microbiology, 6 (7), 651-662. (doi:10.1111/j.1462-5822.2004.00392.x).

Record type: Article

Abstract

The major porin proteins present in the outer membrane of Neisseria meningitidis, the causative agent of life-threatening meningitis and septicaemia, are believed to have potent immunostimulatory effects. In this study, the interactions between human monocyte-derived dendritic cells (mo-DC) and the PorA porin were investigated, in order to reveal the role of this protein in promoting innate and adaptive immune responses. Recombinant (r)PorA induced mo-DC maturation, as reflected by reduced receptor-mediated endocytosis, increased production of the chemokines IL-8, RANTES, MIP-1? and MIP-1? and augmented expression of the surface markers CD40, CD54, CD80, CD86 and major histocompatibility complex class II molecules. However, rPorA induced either low level or no significant secretion of pro-inflammatory cytokines from mo-DC. The protein potently augmented the capacity of mo-DC to activate both allogeneic CD4+ memory T-cells and CD4+RA+ naïve T-cells. In addition, rPorA appeared to inhibit the production of IL-12p70 that follows from the interaction between CD40 on the mo-DC and CD40-ligand on T-cells, thereby directing T-cell differentiation towards a Th2 type response. These data demonstrate that PorA is involved in DC activation and in influencing the nature of the T-helper immune response, which are important properties for generating antibody responses required for protective immunity against meningococci and for determining the immuno-adjuvant effects of this protein.

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Published date: 2004

Identifiers

Local EPrints ID: 26903
URI: http://eprints.soton.ac.uk/id/eprint/26903
ISSN: 1462-5814
PURE UUID: 3ced09ca-be75-41ff-b3ca-ceab04e3e154
ORCID for Judith Holloway: ORCID iD orcid.org/0000-0002-2268-3071
ORCID for Myron Christodoulides: ORCID iD orcid.org/0000-0002-9663-4731

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Date deposited: 25 Apr 2006
Last modified: 18 Feb 2021 16:54

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