Characterization of Humoral and Cellular Immune Responses Elicited by Meningococcal Carriage

Robinson, Karen; Neal, Keith; Howard, C R; Stockton, Joanne; Atkinson, Kieran; Scarth, E.; Morán, Julio; Robins, Adrian; Todd, Ian; Kaczmarski, Edward B.; Gray, Stephen J.; Muscat, Ivan; Slack, R. C. B.; Ala’Aldeen, Dlawer A. A.

doi:10.1128/iai.70.3.1301-1309.2002

Cited by 39 publications

(42 citation statements)

References 53 publications

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“…Mucosal IgA responses to whole N. meningitidis cells and to PorA have also been detected (43,44). We demonstrated the presence of high levels of IgG antibodies specific for the homologous PorA variant in the majority of persistent carriers and high levels of anti-CapY specific IgG antibodies (Table 2 and Fig.…”

Section: Discussionsupporting

confidence: 56%

Phase Variation Mediates Reductions in Expression of Surface Proteins during Persistent Meningococcal Carriage

et al. 2014

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Persistent carriage was associated with high levels of specific IgG antibodies and serum bactericidal activity while recent strain acquisition correlated with a significant induction of antibodies. We conclude that phase-variable genes are driven into lower expression states during long-term persistent meningococcal carriage, in part due to continuous exposure to antibody-mediated selection, suggesting localized hypermutation has evolved to facilitate host persistence.

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Section: Discussionsupporting

confidence: 56%

Phase Variation Mediates Reductions in Expression of Surface Proteins during Persistent Meningococcal Carriage

et al. 2014

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“…Nm is carried by ϳ10% of the population at any one time (12). Asymptomatic carriage primes an adaptive immune response within 2 wk of colonization (13) and is associated with increased titers of salivary IgA (14) and serum IgG (15). We have demonstrated the presence of memory T cell responses to Nm outer membrane vesicles (OMV) in human palatine tonsils (PT) which increase with age (16).…”

mentioning

confidence: 99%

Absence of Mucosal Immunity in the Human Upper Respiratory Tract to the Commensal Bacteria Neisseria lactamica but Not Pathogenic Neisseria meningitidis during the Peak Age of Nasopharyngeal Carriage

Vaughan

Gorringe²,

Davenport

et al. 2009

The Journal of Immunology

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The normal flora that colonizes the mucosal epithelia has evolved diverse strategies to evade, modulate, or suppress the immune system and avoid clearance. Neisseria lactamica and Neisseria meningitidis are closely related obligate inhabitants of the human upper respiratory tract. N. lactamica is a commensal but N. meningitidis is an opportunistic pathogen that occasionally causes invasive disease such as meningitis and septicemia. We demonstrate that unlike N. meningitidis, N. lactamica does not prime the development of mucosal T or B cell memory during the peak period of colonization. This cannot be explained by the induction of peripheral tolerance or regulatory CD4+CD25+ T cell activity. Instead, N. lactamica mediates a B cell-dependent mitogenic proliferative response that is absent to N. meningitidis. This mitogenic response is associated with the production of T cell-independent polyclonal IgM that we propose functions by shielding colonizing N. lactamica from the adaptive immune system, maintaining immunological ignorance in the host. We conclude that, in contrast to N. meningitidis, N. lactamica maintains a commensal relationship with the host in the absence of an adaptive immune response. This may prolong the period of susceptibility to colonization by both pathogenic and nonpathogenic Neisseria species.

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“…Although Neisseria meningitidis is carried in the nasopharynx of between 5 and 40% of individuals (4 -6), the development of meningococcal disease is rare, particularly in adults over 25 years (6,7).…”

mentioning

confidence: 99%

“…Although poorly understood, natural immunization is thought to occur through prolonged or intermittent colonization at the mucosal surface by N. meningitidis or related organisms such as Neisseria lactamica (5)(6)(7)(8). Mucosal as well as systemic immune mechanisms have been implicated in this process (6,9), with both serum and salivary Abs demonstrated following meningococcal carriage (6, 10 -12). Complement-fixing IgG Abs that are high in bactericidal activity (serum bactericidal Abs; SBA 4 ) are thought to be important mediators of protective immunity against N. meningitidis (13).…”

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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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Characterization of Humoral and Cellular Immune Responses Elicited by Meningococcal Carriage

Cited by 39 publications

References 53 publications

Phase Variation Mediates Reductions in Expression of Surface Proteins during Persistent Meningococcal Carriage

Phase Variation Mediates Reductions in Expression of Surface Proteins during Persistent Meningococcal Carriage

Absence of Mucosal Immunity in the Human Upper Respiratory Tract to the Commensal Bacteria Neisseria lactamica but Not Pathogenic Neisseria meningitidis during the Peak Age of Nasopharyngeal Carriage

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

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