Neonatal Exposure to Pneumococcal Phosphorylcholine Modulates the Development of House Dust Mite Allergy during Adult Life

Abstract

Currently, approximately 20% of the global population suffers from an allergic disorder. Allergies and asthma occur at higher rates in developed and industrialized countries. It is clear that many human atopic diseases are initiated neonatally, and herald more severe IgE-mediated disorders, including allergic asthma, which is driven by the priming of TH2 effector T cells. The “hygiene hypothesis” attempts to link the increased excessively sanitary conditions early in life, to a default TH2 response and increasing allergic phenomena. Despite the substantial involvement of IgE antibodies in such conditions, little attention has been paid to the effects of early microbial exposure on the B cell repertoire prior to the initiation of these diseases. Here, we use antibody-binding assays to demonstrate that Streptococcus pneumoniae and house dust mite (HDM) bear similar phosphorylcholine (PC) epitopes. Neonatal C57BL/6 mice immunized with a PC-bearing pneumococcal vaccine expressed increased frequencies of PC-specific B cells in the lungs following sensitizing exposure to HDM as adults. Anti-PC IgM antibodies in the lung decreased the interaction of HDM with pulmonary APCs and were affiliated with lowered allergy-associated cell infiltration into the lung, IgE production, development of airway hyperresponsiveness, and TH2 T cell priming. Thus, exposure of neonatal mice to PC-bearing pneumococci significantly reduced the development of HDM-induced allergic disease during adult life. Our findings demonstrate that B cells generated against conserved epitopes expressed by bacteria, encountered early in life, are also protective against the development of allergic disease during adult life.

Pulmonary α-1,3-Glucan–Specific IgA-Secreting B Cells Suppress the Development of Cockroach Allergy

“…Despite a robust antibody response, B6.Igh-C a mice immunized with MK7 as adults are not protected against allergic disease. These results are similar to our findings in the A. fumigatus fungal and HDM allergy models (15, 16), in which there was a striking age-related dependence for vaccination to induce effective protection against allergic reactions. A similar age-related effect has also been shown to be critical for the induction of iBALT (44).…”

“…Having demonstrated that environmental allergens, such as A. fumigatus and HDM, display antibody-reactive epitopes associated with certain bacteria (15, 16), we expanded our studies to analyze German cockroach ( Blattella germanica ) allergen. Cockroach particles were bound by purified monoclonal anti-α-1,3-glucan antibody, A16 (IgM,λ1) (Figure 1A).…”

“…Exposure to particular bacterial antigens during early life can alter the numbers of these developing clones and permanently select them in to the adult repertoire (9). We have previously demonstrated that altered antigen-specific B cell responses, following neonatal immunization with bacterial vaccines containing polysaccharide or phospholipid moieties shared by Aspergillus fumigatus fungi or house dust mite (HDM), suppress allergic disease development in adult animals (15, 16). …”

Lipopolysaccharide Attenuates Induction of Proallergic Cytokines, Thymic Stromal Lymphopoietin, and Interleukin 33 in Respiratory Epithelial Cells Stimulated with PolyI:C and Human Parechovirus

“…Although, the inhibitory effect of all these LPS on polyI:C were observed, but the implication of the pathogenic bacteria infection in allergy remains to be explored. Moreover, determining whether the inhibitory effect of LPS could be demonstrated with other bacterial components, such as peptidoglycan, teichoic acid, or phosphorylcholine in airway epithelial cells would be of interest (85). …”

A Hard(y) Look at B-1 Cell Development and Function

“…They showed that injection of α1-3 dextran permanently altered the repertoire of carbohydrate-reactive B cells when given within a short window after birth, but not later (summarized in (62)). This antigen is known to activate B-1 cells (63), and is expressed on Aspergillus fumigatus as well as house dust mites, While immunization did not change anti- α1-3 dextran serum IgM levels, it expanded the repertoire of polysaccharide-specific B cells and protected the mice from increased airway reactivity and signs of TH2-mediated airway disease (64). In addition, recent studies suggested that a portion of mainly B-1 cell-derived maternal IgG3 antibodies binds to gut microbiota and is induced in a TLR-dependent manner (65).…”