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

Abstract

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.

Teleost skin, an ancient mucosal surface that elicits gut-like immune responses

“…Mammalian sIgA plays a key role in immune exclusion by coating a portion of the bacterial microbiota of the gut (17),skin (25), mouth (26), nose (27), and vagina (28). Except for the gut, it is unclear whether sIgA is the main Ig isotype participating in the bacterial coating of the microbiota at the other mucosal surfaces.…”

Polysaccharide-Specific Memory B Cells Predict Protection against Experimental Human Pneumococcal Carriage

“…We did not observe an association between the number in 6BPS IgA-secreting B-cell populations and protection against carriage acquisition, indicating that the peripheral assessment of IgA-secreting populations may not reflect the activity of IgA populations at the mucosa. IgA1 accounts for approximately 90% of all IgA found in peripheral blood and the upper respiratory tract (23,24). S. pneumoniae is able to cleave IgA1, via IgA1 protease, a mechanism that facilitates pneumococcal adherence to the epithelium and abrogates the protective effects of IgA (25).…”

Isolation and Detection of Human IgA Using a Streptococcal IgA-Binding Peptide

“…These had been produced, characterized (44), and donated by Dr. H. Baxendale (Institute of Child Health, London, U.K.). Human colostral S-IgA1 and S-IgA2, purified by the use of jacalin agarose as described (43), was used for standardization of subclassspecific assays of salivary IgA.…”