Analysis of Neisseria lactamica antigens putatively implicated in acquisition of natural immunity to Neisseria meningitidis

Troncoso, G

doi:10.1016/s0928-8244(02)00326-7

Cited by 12 publications

(19 citation statements)

References 22 publications

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“…This may be explained by the location of T cell epitopes largely within the conserved region of meningococcal OMP, enabling cross-reactivity to other serosubtypes (70,71). Alternatively, the cross-reactive immunity may be induced by carriage of related commensal species such as N. lactamica (8,72), which typically colonizes earlier in childhood than N. meningitidis (73) and does not express PorA (72). Indeed, our detection of responses to mutant OMV without PorA (data not shown) suggests that other OMP such as PorB, Rmp, Opc, Opa, Tbps, or OMP85 are involved in the T cell stimulation (9, 24).…”

Section: Discussionmentioning

confidence: 99%

Evidence for Naturally Acquired T Cell-Mediated Mucosal Immunity to Neisseria meningitidis

Davenport

Guthrie

Findlow

et al. 2003

The Journal of Immunology

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Naturally acquired protective immunity against Neisseria meningitidis is thought to partially explain the disparity between the high levels of carriage in the human nasopharynx and the rare incidence of disease. To investigate this immunity to Neisseria meningitidis at the mucosal level, in vitro cellular responses to outer membrane vesicle preparations derived from this pathogen were examined using mononuclear cells from the palatine tonsils of adults and children. Characterization of these responses was achieved by depletion of CD45RA+, CD45RO+, and CD19+ populations and outer membrane vesicles derived from isogenic mutants expressing different serosubtypes of the major outer membrane protein, porin A (PorA), no PorA and membrane preparations from a mutant with no LPS (LpxA−). The magnitude of cellular proliferative responses against the outer membrane vesicles were strongly associated with age and were largely T cell mediated, involving both CD45RO+ and CD45RA+ T cell phenotypes. Responses were not dependent on LPS but consisted of both PorA cross-specific and non-PorA-dependent responses. Cellular immunity against Neisseria meningitidis was found to be frequently associated with systemic IgG Abs but was not associated with serum bactericidal Abs. For the first time our results demonstrate an age-associated acquisition of mucosal T effector/memory cell responses to Neisseria meningitidis. This mucosal cellular immunity can be present in the absence of serum bactericidal Abs, a classical marker of protective immunity.

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Section: Discussionmentioning

confidence: 99%

Evidence for Naturally Acquired T Cell-Mediated Mucosal Immunity to Neisseria meningitidis

Davenport

Guthrie

Findlow

et al. 2003

The Journal of Immunology

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“…Purified Nlac PorB was first examined by SDS-PAGE followed by Coomassie staining ( Figure 1A) and it appears to have a m.w. of approximately 35-37 kDa (indicated by the arrow) in reducing conditions (monomeric form) [61,62]. Higher molecular weight bands corresponding to trimers and oligomers were detected by non-denaturing gel electrophoresis performed in the absence of SDS (data not shown), suggesting a presumed native trimeric structure similar to Nme PorB [56].…”

Section: Purification Of Porb From N Lactamicamentioning

confidence: 94%

The PorB porin from commensal Neisseria lactamica induces Th1 and Th2 immune responses to ovalbumin in mice and is a potential immune adjuvant

Liu

Wetzler

Massi

2008

Vaccine

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Porins from pathogenic Neisseriae are among several bacterial products with immune adjuvant activity. N. meningitidis (Nme) PorB, has been shown to induce immune cells activation in a TLR2-dependent manner and acts as a vaccine immune adjuvant. The PorB porin from Neisseria lactamica (Nlac), a common nasopharyngeal commensal shares significant structural and functional similarities with Nme PorB. In this work we ask whether the immune adjuvant ability of porins from pathogenic Neisserial strains is a characteristic shared with porins from non-pathogenic Neisserial species or whether it is unique for bacterial products derived from microorganisms capable of inducing inflammation and disease. We evaluate the potential immune adjuvant effect of Nlac PorB in mice using ovalbumin (OVA) as a prototype antigen. Immunization with Nlac PorB/OVA induced high OVA-specific IgG and IgM titers compared to OVA alone, similar to other adjuvants such as Nme PorB and alum. High titers of IgG1 and IgG2b were detected as well as production of IL-4, IL-10, IL-12 and INF-γ in response to Nlac PorB, consistent with induction of both a Th1-type and a Th2-type immune response. OVA-specific proliferation was also determined in splenocytes from Nlac PorB/OVA immunized mice. In addition, B cell activation in vitro and cytokine production in response to Nlac PorB was found to be mediated by TLR2, in a similar manner to Nme PorB.

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“…One protein that could be involved in the induction of cross-protective immune responses is the N. lactamica porin (Troncoso et al , 2002). Porins, which are essential for growth, are pore-forming membrane proteins that create channels, allowing transport of hydrophilic molecules across lipid bilayers (Achouak et al , 2001) and are generally highly expressed.…”

Section: Introductionmentioning

confidence: 99%

Variation in the Neisseria lactamica porin, and its relationship to meningococcal PorB

et al. 2008

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One potential vaccine strategy in the fight against meningococcal disease involves the exploitation of outer-membrane components of Neisseria lactamica, a commensal bacterium closely related to the meningococcus, Neisseria meningitidis. Although N. lactamica shares many surface structures with the meningococcus, little is known about the antigenic diversity of this commensal bacterium or the antigenic relationships between N. lactamica and N. meningitidis. Here, the N. lactamica porin protein (Por) was examined and compared to the related PorB antigens of N. meningitidis, to investigate potential involvement in anti-meningococcal immunity. Relationships among porin sequences were determined using distance-based methods and FST, and maximum-likelihood analyses were used to compare the selection pressures acting on the encoded proteins. These analyses demonstrated that the N. lactamica porin was less diverse than meningococcal PorB and although it was subject to positive selection, this was not as strong as the positive selection pressures acting on the meningococcal porin. In addition, the N. lactamica porin gene sequences and the protein sequences of the loop regions predicted to be exposed to the human immune system were dissimilar to the corresponding sequences in the meningococcus. This suggests that N. lactamica Por, contrary to previous suggestions, may have limited involvement in the development of natural immunity to meningococcal disease and might not be effective as a meningococcal vaccine component.

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Analysis of Neisseria lactamica antigens putatively implicated in acquisition of natural immunity to Neisseria meningitidis

Cited by 12 publications

References 22 publications

Evidence for Naturally Acquired T Cell-Mediated Mucosal Immunity to Neisseria meningitidis

Evidence for Naturally Acquired T Cell-Mediated Mucosal Immunity to Neisseria meningitidis

The PorB porin from commensal Neisseria lactamica induces Th1 and Th2 immune responses to ovalbumin in mice and is a potential immune adjuvant

Variation in the Neisseria lactamica porin, and its relationship to meningococcal PorB

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