Molecular biology and vaccine aspects of bacterial immunoglobulin A1 proteases

Lomholt, Hans

doi:10.1111/j.1600-0463.1996.tb05580.x

Cited by 9 publications

(9 citation statements)

References 111 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As this situation is most likely to occur in early life (28), samples of nasal wash were collected from the child at regular intervals of 2 weeks. IgA1 protease-producing H. influenzae was isolated from one of nine samples (Table 3).…”

Section: Resultsmentioning

confidence: 99%

Immunoglobulins in Nasal Secretions of Healthy Humans: Structural Integrity of Secretory Immunoglobulin A1 (IgA1) and Occurrence of Neutralizing Antibodies to IgA1 Proteases of Nasal Bacteria

Kirkeby¹,

Rasmussen²,

Reinholdt

et al. 2000

Clin Diagn Lab Immunol

View full text Add to dashboard Cite

Certain bacteria, including overt pathogens as well as commensals, produce immunoglobulin A1 (IgA1) proteases. By cleaving IgA1, including secretory IgA1, in the hinge region, these enzymes may interfere with the barrier functions of mucosal IgA antibodies, as indicated by experiments in vitro. Previous studies have suggested that cleavage of IgA1 in nasal secretions may be associated with the development and perpetuation of atopic disease. To clarify the potential effect of IgA1 protease-producing bacteria in the nasal cavity, we have analyzed immunoglobulin isotypes in nasal secretions of 11 healthy humans, with a focus on IgA, and at the same time have characterized and quantified IgA1 protease-producing bacteria in the nasal flora of the subjects. Samples in the form of nasal wash were collected by using a washing liquid that contained lithium as an internal reference. Dilution factors and, subsequently, concentrations in undiluted secretions could thereby be calculated. IgA, mainly in the secretory form, was found by enzyme-linked immunosorbent assay to be the dominant isotype in all subjects, and the vast majority of IgA (median, 91%) was of the A1 subclass, corroborating results of previous analyses at the level of immunoglobulin-producing cells. Levels of serum-type immunoglobulins were low, except for four subjects in whom levels of IgG corresponded to 20 to 66% of total IgA. Cumulative levels of IgA, IgG, and IgM in undiluted secretions ranged from 260 to 2,494 (median, 777) g ml ؊1 . IgA1 protease-producing bacteria (Haemophilus influenzae, Streptococcus pneumoniae, or Streptococcus mitis biovar 1) were isolated from the nasal cavities of seven subjects at 2.1 ؋ 10 3 to 7.2 ؋ 10 6 CFU per ml of undiluted secretion, corresponding to 0.2 to 99.6% of the flora. Nevertheless, ␣-chain fragments characteristic of IgA1 protease activity were not detected in secretions from any subject by immunoblotting. Neutralizing antibodies to IgA1 proteases of autologous isolates were detected in secretions from five of the seven subjects but not in those from two subjects harboring IgA1 protease-producing S. mitis biovar 1. ␣-chain fragments different from Fc ␣ and Fd ␣ were detected in some samples, possibly reflecting nonspecific proteolytic activity of microbial or host origin. These results add to previous evidence for a role of secretory immunity in the defense of the nasal mucosa but do not help identify conditions under which bacterial IgA1 proteases may interfere with this defense.

show abstract

Section: Resultsmentioning

confidence: 99%

Immunoglobulins in Nasal Secretions of Healthy Humans: Structural Integrity of Secretory Immunoglobulin A1 (IgA1) and Occurrence of Neutralizing Antibodies to IgA1 Proteases of Nasal Bacteria

Kirkeby¹,

Rasmussen²,

Reinholdt

et al. 2000

Clin Diagn Lab Immunol

View full text Add to dashboard Cite

show abstract

“…Circumstantial evidence related to the unique association of IgA1 proteases with human pathogenic bacterial species (9,6) suggests that this enzyme plays a significant role in pathogenesis. IgA1 proteases are produced by a variety of gram-positive and gram-negative human pathogens (10)(11)(12). Among those, the IgA1 proteases of the pathogenic Neisseriae and various Haemophilus species are structurally closely related (13,14).…”

mentioning

confidence: 99%

Immunoglobulin A1 Protease, an Exoenzyme of Pathogenic Neisseriae, Is a Potent Inducer of Proinflammatory Cytokines

Lorenzen

Düx

Wölk

et al. 1999

The Journal of Experimental Medicine

View full text Add to dashboard Cite

A characteristic of human pathogenic Neisseriae is the production and secretion of an immunoglobulin (Ig)A1-specific serine protease (IgA1 protease) that cleaves preferentially human IgA1 and other target proteins. Here we show a novel function for native IgA1 protease, i.e., the induction of proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-8 from peripheral blood mononuclear cells. The capacity of IgA1 protease to elicit such cytokine responses in monocytes was enhanced in the presence of T lymphocytes. IgA1 protease did not induce the regulatory cytokine IL-10, which was, however, found in response to lipopolysaccharide and phytohemagglutinin. The immunomodulatory effects caused by IgA1 protease require a native form of the enzyme, and denaturation abolished cytokine induction. However, the proteolytic activity is not required for the cytokine induction by IgA1 protease. Our results indicate that IgA1 protease exhibits important immunostimulatory properties and may contribute substantially to the pathogenesis of neisserial infections by inducing large amounts of TNF-α and other proinflammatory cytokines. In particular, IgA1 protease may represent a key virulence determinant of bacterial meningitis.

show abstract

“…To date no animal has been identified that is infected by pathogenic bacteria producing IgA 1 proteases, or whose endogenous microbiota contains bacteria that produce IgA 1 proteases that cleave the animals own IgA (14). Therefore, there is no animal model to study the planktonic phase compared to the substratum were not addressed in these experiments.…”

mentioning

confidence: 99%

Effect of IgA1 Protease on the Ability of Secretory IgA1 Antibodies to Inhibit the Adherence of Streptococcus mutans

Tyler

Cole

1998

Microbiology and Immunology

View full text Add to dashboard Cite

Secretory IgA (SIgA) is the principal immunoglobulin isotype present in the mucosal secretions of humans. SIgA is thought to play a major role in host defense at these surfaces by inhibiting the colonization of potentially pathogenic microorganisms. A number of bacteria that are mucosal pathogens of humans produce a protease that specifically cleaves the IgA1 subclass of humans and great apes at the hinge region to produce Fab and Fc fragments. In order to study the effect of IgA1 protease on the ability of SIgA1 antibodies to inhibit bacterial adherence, an in vitro assay that quantifies the adsorption of radiolabeled Streptococcus mutans to hydroxyapatite (HA) beads was employed. High titer S. mutans-specific SIgA1 and SIgA2 antibodies were induced in chimpanzee milk for use in the assay. Faba1 fragments had significantly reduced ability to inhibit adherence of S. mutans to saliva-coated HA compared to intact SIgA1 or SIgA2 anti-S. mutans antibodies. These data support the potential importance of IgA1 proteases as an ecological determinant in the oral cavity and their role as a determinant of pathogenesis of pathogenic bacteria whose portal of entry is the mucosal surface.

show abstract

Molecular biology and vaccine aspects of bacterial immunoglobulin A1 proteases

Cited by 9 publications

References 111 publications

Immunoglobulins in Nasal Secretions of Healthy Humans: Structural Integrity of Secretory Immunoglobulin A1 (IgA1) and Occurrence of Neutralizing Antibodies to IgA1 Proteases of Nasal Bacteria

Immunoglobulins in Nasal Secretions of Healthy Humans: Structural Integrity of Secretory Immunoglobulin A1 (IgA1) and Occurrence of Neutralizing Antibodies to IgA1 Proteases of Nasal Bacteria

Immunoglobulin A1 Protease, an Exoenzyme of Pathogenic Neisseriae, Is a Potent Inducer of Proinflammatory Cytokines

Effect of IgA1 Protease on the Ability of Secretory IgA1 Antibodies to Inhibit the Adherence of Streptococcus mutans

Contact Info

Product

Resources

About