Th2-associated immunity to bacteria in teenagers and susceptibility to asthma

Abstract

Bacterial colonisation of the airways is associated with increased risk of childhood asthma. Immunoglobulin (Ig)E against bacterial antigens has been reported in some asthmatics, suggesting a role for bacterial-specific type-2 immunity in disease pathogenesis. We aimed to investigate relationships between bacterial-specific IgE amongst teenagers and asthma susceptibility.We measured titres of IgE against Haemophilus influenzae, Streptococcus pneumoniae and Staphylococcus aureus in 1,380 teenagers, and related these to asthma symptomatology and immunophenotypes.IgE titres against S. aureus-derived enterotoxins were highest amongst atopics and were associated with asthma risk. Surprisingly, IgE titres against H. influenzae and S. pneumoniae surface antigens were higher, not stratified by atopy and independently associated with decreased asthma risk.The positive association between type-2 immunity to S. aureus and asthma phenotypes probably reflects IgE-mediated effector cell activation via enterotoxin super antigens which are secreted in soluble form. The contrasting benign nature of type-2 immunity to H. influenzae and S. pneumoniae antigens may reflect their lower availability in soluble forms that can crosslink IgE receptors. We theorise that instead they may be processed by antigen presenting cells and presented to type-2 memory cells leading to mucosal secretion of interleukin (IL)-4/IL-13, a mechanism widely recognised in other tissues to attenuate T-helper-1 associated bacterialinduced inflammation.

Do bacteria have a role in asthma development?

“…The levels of IgE antibodies to H. influenzae and S. pneumonia were very low in this study. Furthermore, the findings do not agree with the previous report discussed previously showing a positive relationship between IgE to H. influenzae and S. pneumonia with atopy [16,19]. Future studies will have to elucidate a potential dualistic role of Th2 responses as proposed by the authors.…”

“…IgE antibodies towards bacterial antigens have also been described previously. Specific IgE to H. influenzae and S. pneumonia have been found in the serum of approximately a third of atopic children and asthmatic adults, but unlike in the study by HOLLAMS et al [16] they were all related to a subject's atopic status [19].…”

“…As HOLLAMS et al [16] discuss there is some evidence that Th2 cytokines may suppress other pro-inflammatory cytokines, such as tumour necrosis factor-a and IL-1, as well as pro-inflammatory mediators such as prostaglandin, thereby counter regulating increased Th1 immune responses [21]. Thus, bacterial IgE to H. influenzae and S. pneumonia surface antigens might merely reflect such a downregulating Th2 response and may be regarded as a marker for an overall balanced immune response towards airway colonising bacteria.…”

“…In this issue of the European Respiratory Journal, HOLLAMS et al [16] report an association between asthma and levels of specific IgE antibodies against S. aureus enterotoxin (SAE) and surface antigens of H. influenzae and S. pneumonia. It has previously been shown that IgE antibodies are not only directed towards inhalant and food allergens, but also towards microbes.…”

“…In the study by HOLLAMS et al [16] a positive association between IgE levels against SAE and an inverse relationship between IgE levels to H. influenzae and S. pneumonia surface antigens and asthma in a cohort of 1,380 teenagers is reported. At first glance, these findings may suggest that a subject's IgE immune response may be indicative of harmful and protective bacterial exposures for the development of asthma.…”