Natural human antibodies to pneumococcus have distinctive molecular characteristics and protect against pneumococcal disease

Baxendale, Helen; Johnson, Marina; Stephens, Robert; Yuste, José; Klein, Nigel; Brown, Jeremy S.; Green, David

doi:10.1111/j.1365-2249.2007.03535.x

Cited by 64 publications

(51 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Some IgM antibodies that are protective against bacterial infections bind many unrelated antigens, such as singlestranded DNA, thyroglobulin, and ␤-galactosidase (27). Such IgM antibodies, which are called polyreactive or natural antibodies, are found in preimmune sera (3,27,49,50) and have been isolated as hybridomas producing anti-PPS antibody (6). Also, the level of natural antibodies has been shown to decrease with age (10).…”

Section: Discussionmentioning

confidence: 99%

Older Adults Have a Low Capacity To Opsonize Pneumococci Due to Low IgM Antibody Response to Pneumococcal Vaccinations

2011

View full text Add to dashboard Cite

Since the 23-valent pneumococcal polysaccharide vaccine (PPV23) is less effective for older adults than for young adults, it is important to investigate the immunologic basis for the reduced efficacy of PPV23 among older adults. We determined the effectiveness of PPV23 among young (n ‫؍‬ 55) and older (n ‫؍‬ 44) adults by measuring the serum IgG, IgM, and IgA concentrations and opsonic capacities against serotypes 14, 18C, and 23F. While young and older adults showed no difference in levels of IgG antibodies against pneumococcal polysaccharide (PPS), older adults had lower IgA and IgM antibody levels than young adults for all three serotypes. In both age groups, anti-PPS IgA or IgM antibody levels were much lower than anti-PPS IgG antibody levels. Young adults showed higher opsonic capacities than older adults for serotypes 14 and 23F. In order to determine the effects of anti-PPS IgA or IgM antibodies on the functional difference between young and older adults, anti-PPS IgA or IgM antibodies were removed from immune sera by affinity chromatography. The difference in opsonic capacity between young and older adults disappeared for serotypes 14 and 23F (but not for serotype 18C) when IgM antibody was removed. However, there was no significant difference between the two age groups when IgA antibody was removed. In conclusion, even though anti-PPS IgG antibody levels are high compared with anti-PPS IgM antibody levels, the low levels of anti-PPS IgM antibody alone can explain the functional difference observed between young and older adults immunized with PPV23 with regard to some pneumococcal serotypes.

show abstract

Section: Discussionmentioning

confidence: 99%

Older Adults Have a Low Capacity To Opsonize Pneumococci Due to Low IgM Antibody Response to Pneumococcal Vaccinations

2011

View full text Add to dashboard Cite

show abstract

“…The classical complement pathway is activated by specific immunoglobulin G (IgG) and was generally considered an effector of the adaptive immune response, but recent data have demonstrated an important role for the classical pathway as part of the innate immune response to S. pneumoniae. S. pneumoniae cell wall phosphorylcholine (PC) is recognized by the serum proteins C-reactive protein (CRP) and serum amyloid P (SAP) (collectively termed pentraxins due to their structurally similarity) (40) and also by natural IgM (4). In addition, the cell surface lectin SIGN-R1 binds to the S. pneumoniae capsule (20).…”

mentioning

confidence: 99%

TheStreptococcuspneumoniaeCapsule Inhibits Complement Activity and Neutrophil Phagocytosis by Multiple Mechanisms

et al. 2010

View full text Add to dashboard Cite

The Streptococcus pneumoniae capsule is vital for virulence and may inhibit complement activity and phagocytosis. However, there are only limited data on the mechanisms by which the capsule affects complement and the consequences for S. pneumoniae interactions with phagocytes. Using unencapsulated serotype 2 and 4 S. pneumoniae mutants, we have confirmed that the capsule has several effects on complement activity. The capsule impaired bacterial opsonization with C3b/iC3b by both the alternative and classical complement pathways and also inhibited conversion of C3b bound to the bacterial surface to iC3b. There was increased binding of the classical pathway mediators immunoglobulin G (IgG) and C-reactive protein (CRP) to unencapsulated S. pneumoniae, indicating that the capsule could inhibit classical pathway complement activity by masking antibody recognition of subcapsular antigens, as well as by inhibiting CRP binding. Cleavage of serum IgG by the enzyme IdeS reduced C3b/iC3b deposition on all of the strains, but there were still marked increases in C3b/iC3b deposition on unencapsulated TIGR4 and D39 strains compared to encapsulated strains, suggesting that the capsule inhibits both IgG-mediated and IgG-independent complement activity against S. pneumoniae. Unencapsulated strains were more susceptible to neutrophil phagocytosis after incubation in normal serum, normal serum treated with IdeS, complement-deficient serum, and complement-deficient serum treated with IdeS or in buffer alone, suggesting that the capsule inhibits phagocytosis mediated by Fc␥ receptors, complement receptors, and nonopsonic receptors. Overall, these data show that the S. pneumoniae capsule affects multiple aspects of complement-and neutrophil-mediated immunity, resulting in a profound inhibition of opsonophagocytosis.The Gram-positive pathogen Streptococcus pneumoniae is one of the most common causes of pneumonia, septicemia, and meningitis in children and adults in both industrialized and developing parts of the world (10). This large burden of disease is compounded by the increased incidence of S. pneumoniae infections associated with HIV and by increasing antibiotic resistance among clinical isolates, and there is a strong need to understand the molecular pathogenesis of S. pneumoniae infections to assist the development of new therapeutic targets. Probably the most important virulence factor for S. pneumoniae is the extracellular capsule, a layer consisting of chains of monosaccharides that surrounds the bacteria. For S. pneumoniae strains, there are 91 antigenically distinct capsular serotypes, dictated by the order and type of the monosaccharide units within the polysaccharide chain and by different side branches (5, 27). The importance of the S. pneumoniae capsule for virulence is demonstrated by the facts that (i) all clinical isolates causing invasive disease are encapsulated; (ii) loss of the capsule by either genetic mutation or enzymatic degradation dramatically reduces S. pneumoniae virulence in animal models of infection ...

show abstract

“…In this cell population, it is possible that endogenous antigen binding may provide the essential survival signal, adequate to prevent clonal deletion, but not strong enough to induce Ab production and cell cycling. 48 For this second signal, macrophage and stromal cell factors in the microenvironment seem to be crucial, which may also be relevant for the still elusive CLL precursor. 49 In conclusion, we provide evidence for signaling incompetence with antigen alone in a unique cognate BcR-ligand setting relevant for CLL subset #1, a large and clinically aggressive stereotyped CLL subset.…”

Section: Discussionmentioning

confidence: 99%

Silenced B-cell receptor response to autoantigen in a poor-prognostic subset of chronic lymphocytic leukemia

et al. 2014

View full text Add to dashboard Cite

show abstract

Natural human antibodies to pneumococcus have distinctive molecular characteristics and protect against pneumococcal disease

Cited by 64 publications

References 62 publications

Older Adults Have a Low Capacity To Opsonize Pneumococci Due to Low IgM Antibody Response to Pneumococcal Vaccinations

Older Adults Have a Low Capacity To Opsonize Pneumococci Due to Low IgM Antibody Response to Pneumococcal Vaccinations

TheStreptococcuspneumoniaeCapsule Inhibits Complement Activity and Neutrophil Phagocytosis by Multiple Mechanisms

Silenced B-cell receptor response to autoantigen in a poor-prognostic subset of chronic lymphocytic leukemia

Contact Info

Product

Resources

About