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Published on: April 2, 2014
Effect of microbial heat shock proteins on airway inflammation and hyperresponsiveness
Yeong-Ho Rha1, Christian Taube, Angela Haczku
1Division of Cell Biology, Department of Pediatrics, National Jewish Medical and Research Center, Denver, CO 80206, USA.
Abstract:
Microbial heat shock proteins (hsp) have been associated with the generation and induction of Th1-type immune responses. We tested the effects of treatment with five different microbial hsp (Mycobacterium leprae, Streptococcus pneumoniae, Helicobacter pylori, bacillus Calmette-Guérin, and Mycobacterium tuberculosis) in a murine model of allergic airway inflammation and airway hyperresponsiveness (AHR). Mice were sensitized to OVA by i.p. injection and then challenged by OVA inhalation. Hsp were administered to each group by i.p. injection before sensitization and challenge. Sensitized and challenged mice developed increased serum levels of OVA-specific IgE with significant airway eosinophilia and heightened responsiveness to methacholine when compared with nonsensitized animals. Administration of M. leprae hsp prevented both development of AHR as well as bronchoalveolar lavage fluid eosinophilia in a dose-dependent manner. Treatment with M. leprae hsp also resulted in suppression of IL-4 and IL-5 production in bronchoalveolar lavage fluid, while IL-10 and IFN-gamma production were increased. Furthermore, M. leprae hsp treatment significantly suppressed OVA-specific IgE production and goblet cell hyperplasia/mucin hyperproduction. In contrast, treatment with the other hsp failed to prevent changes in airway responsiveness, lung eosinophilia, or cytokine production. Depletion of gamma/delta T lymphocytes before sensitization and challenge abolished the effect of M. leprae hsp treatment on AHR. These results indicate selective and distinctive properties among the hsp, and that M. leprae hsp may have a potential therapeutic role in the treatment of allergic airway inflammation and altered airway function.
Insights
Microbial heat shock proteins (hsp) from Mycobacterium leprae show potential in treating allergic airway inflammation. This specific hsp prevented airway hyperresponsiveness and reduced eosinophil counts in a mouse model.
Area of Science:
- Immunology
- Allergy Research
- Microbial Protein Research
Background:
- Microbial heat shock proteins (hsp) are linked to Th1 immune responses.
- Allergic airway inflammation and airway hyperresponsiveness (AHR) are significant health concerns.
- Investigating microbial hsp for therapeutic potential in allergic diseases is warranted.
Purpose of the Study:
- To evaluate the effects of five microbial heat shock proteins (hsp) on a murine model of allergic airway inflammation and AHR.
- To determine if M. leprae hsp has a therapeutic effect on established allergic airway inflammation.
Main Methods:
- A mouse model of allergic airway inflammation was established using ovalbumin (OVA) sensitization and challenge.
- Mice received intraperitoneal injections of five different microbial hsp prior to sensitization and challenge.
- Key markers of allergic inflammation, including IgE levels, eosinophilia, methacholine responsiveness, and cytokine profiles, were assessed.
Main Results:
- Administration of Mycobacterium leprae hsp significantly prevented the development of AHR and airway eosinophilia in a dose-dependent manner.
- M. leprae hsp treatment suppressed Th2 cytokines (IL-4, IL-5) and increased Th1 cytokines (IL-10, IFN-gamma) in bronchoalveolar lavage fluid.
- Other microbial hsp tested did not demonstrate significant protective effects against allergic airway inflammation.
- Depletion of gamma/delta T lymphocytes abrogated the protective effect of M. leprae hsp, suggesting their involvement.
Conclusions:
- Mycobacterium leprae hsp exhibits unique properties that can ameliorate allergic airway inflammation and airway hyperresponsiveness.
- M. leprae hsp may represent a novel therapeutic strategy for allergic airway diseases.
- The therapeutic effect of M. leprae hsp appears to be mediated, at least in part, through gamma/delta T lymphocytes.
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