부산대학교 도서관

The establishment of type 2 responses driven by allergic sensitization prior to exposure to helminth parasites has demonstrated how tissue-specific responses can protect against migrating larval stages, but, as a consequence, allow for immune-mediated, parasite/allergy-associated morbidity. In this way, whether helminth cross-reacting allergen-specific antibodies are produced and play a role during the helminth infection, or exacerbate the allergic outcome awaits elucidation. Thus, the main objective of the study was to investigate whether house dust mite (HDM) sensitization triggers allergen-specific antibodies that interact with Ascaris antigens and mediate antibody-dependent deleterious effects on these parasites as well as, to assess the capacity of cross-reactive helminth proteins to trigger allergic inflammation in house dust mite presensitized mice. Here, we show that the sensitization with HDM-extract drives marked IgE and IgG1 antibody responses that cross-react with Ascaris larval antigens. Proteomic analysis of Ascaris larval antigens recognized by these HDM-specific antibodies identified Ascaris tropomyosin and enolase as the 2 major HDM homologues based on high sequence and structural similarity. Moreover, the helminth tropomyosin could drive Type-2 associated pulmonary inflammation similar to HDM following HDM tropomyosin sensitization. The HDM-triggered IgE cross-reactive antibodies were found to be functional as they mediated immediate hypersensitivity responses in skin testing. Finally, we demonstrated that HDM sensitization in either B cells or FcγRIII alpha-chain deficient mice indicated that the allergen driven cell-mediated larval killing is not antibody-dependent. Taken together, our data suggest that aeroallergen sensitization drives helminth reactive antibodies through molecular and structural similarity between HDM and Ascaris antigens suggesting that cross-reactive immune responses help drive allergic inflammation. Author summary: Epidemiological studies related to the interaction between allergies and helminth infection led to the observations that helped shape the so-called hygiene hypothesis, which generally states that chronic exposure to helminths diminishes the risk of the development of allergic disease. However, there are conflicting studies that have called this particular hypothesis into question, such as, the studies that suggest that infection with the helminth Ascaris lumbricoides is a risk factor for wheezing and atopy or can aggravate the clinical symptoms of asthma. A hypothetical explanation for such phenomenon is the fact that there is a high degree of molecular and structural similarities among helminth antigens with many common allergens, including the house dust mite (HDM). This high degree of homology of certain epitopes shared between helminths and allergens generate cross-react antibodies which may play a role in the pathogenesis or regulation of both conditions. Thus, this study aimed to understand the structural basis for cross-reactive antibodies induced by HDM sensitization. Here, we demonstrate that HDM sensitization drives helminth cross-reactive antibodies through molecular and structural homology between tropomyosins and enolases. This study highlights the pro-allergenic properties of HDM and helminth proteins that share homologous epitopes. [ABSTRACT FROM AUTHOR]