Allergy Asthma Immunol Res.  2014 Jan;6(1):83-88. 10.4168/aair.2014.6.1.83.

A Novel Synthetic Mycolic Acid Inhibits Bronchial Hyperresponsiveness and Allergic Inflammation in a Mouse Model of Asthma

• Kim YJ
• Kim HJ
• Jeong SK
• Lee SH
• Kang MJ
• Yu HS
• Jung YH
• Seo JH
• Kim BJ
• Yu J
• Park SJ
• Lee YC
• Hong SJ

• KMID: 2166946
• DOI: http://doi.org/10.4168/aair.2014.6.1.83

Abstract

PURPOSE
Recognition of microbes is important to trigger the innate immune system. Mycolic acid (MA) is a component of the cell walls of mycobacteria such as Mycobacterium bovis Bacillus Calmette-Guerin. MA has immunogenic properties, which may modulate the innate and adaptive immune response. This study aimed to investigate whether a novel synthetic MA (sMA) inhibits allergic inflammatory responses in a mouse model of asthma.
METHODS
BALB/c mice were injected intraperitoneally with sMA followed by sensitization and challenge with ovalbumin (OVA). Mice were examined for bronchial hyperresponsiveness (BHR), the influx of inflammatory cells into the lung tissues, histopathological changes in the lungs and CD4+CD25+Foxp3+ T cells in the spleen, and examined the response after the depleting regulatory T cells (Tregs) with an anti-CD25mAb.
RESULTS
Treatment of mice with sMA suppressed the asthmatic response, including BHR, bronchoalveolar inflammation, and pulmonary eosinophilic inflammation. Anti-CD25mAb treatment abrogated the suppressive effects of sMA in this mouse model of asthma and totally depleted CD4+CD25+Foxp3+ T cells in the spleen.
CONCLUSIONS
sMA attenuated allergic inflammation in a mouse model of asthma, which might be related with CD4+CD25+Foxp3+ T cell.

Keyword

Mycolic acid; asthma; allergic inflammation; regulatory T cells; mice

MeSH Terms

Adaptive Immunity
Animals
Asthma*
Bacillus
Cell Wall
Eosinophils
Immune System
Inflammation*
Lung
Mice*
Mycobacterium bovis
Mycolic Acids*
Ovalbumin
Spleen
T-Lymphocytes
T-Lymphocytes, Regulatory
Mycolic Acids
Ovalbumin

Figure

• 

  Fig. 1 Treatment of ovalbumin (OVA)-induced allergic asthmatic mice with synthetic mycolic acid (sMA) and effects of anti-CD25 monoclonal antibody (mAb) treatment on the BHR. OVA: mice sensitized with intraperitoneal injections of OVA on Days 0 and 7 and then challenged with aerosolized OVA (1%) on Days 14-16 (a single 30-min challenge per day); Saline: mice sensitized and challenged with saline following the same time schedule described for OVA group; sMA: mice that were injected intraperitoneally with the sMA on 5 days after sensitization and challenge with OVA; Vehicle: mice were injected intraperitoneally with liposome as a control for sMA on 5 days after sensitization and challenge with OVA; sMA + Anti-CD25: mice received sMA plus the anti-CD25 mAb; sMA + Isotype: mice received sMA and rat IgG (isotype) as a control for anti-CD25 mAb. Bronchial hyperresponsiveness (BHR). *P<0.05; **P<0.01 compared to OVA; †P<0.05; ††P<0.01 compared to sMA + Anti-CD25. The values represent the mean±SEM of the results from 5 mice per group.

• 

  Fig. 2 Treatment of OVA-induced allergic asthmatic mice with sMA and effects of anti-CD25 mAb treatment on the differential cell numbers in BAL fluid. The plot legends are as described in Fig. 1. sMA treatment inhibited the number of total cells, macrophages, eosinophils, lymphocytes, and neutrophils in BAL fluid. However, it did not show in vehicle and anti-CD25 mAb treatment. Values represent the mean±SEM of the results from five mice per group. *P<0.05; **P<0.01; ***P=0.05.

• 

  Fig. 3 Treatment of OVA-induced allergic asthmatic mice with sMA and effects of anti-CD25 mAb treatment on the lungs. The lungs were were stained with hematoxylin and eosin. The plot legends are as described in Fig. 1. (A) Lung pathology. (B) Peribronchial and perivascular lung inflammation score. The values represent the mean±SEM of the results from 5 mice per group. *P<0.01.

• 

  Fig. 4 Effect of sMA on the percentage of Foxp3+ Treg cells on the splenocytes. The Treg cell population was totally depleted by the anti-CD25 mAb. The values represent the mean±SEM of the results from 5 mice. *P=0.05.

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