title: Effects of mycobacteria major secretion protein, Ag85B, on allergic inflammation in the lung.
abstract: Many epidemiological studies have suggested that the recent increase in prevalence and severity of allergic diseases such as asthma is inversely correlated with Mycobacterium bovis bacillus Calmette Guerin (BCG) vaccination. However, the underlying mechanisms by which mycobacterial components suppress allergic diseases are not yet fully understood. Here we showed the inhibitory mechanisms for development of allergic airway inflammation by using highly purified recombinant Ag85B (rAg85B), which is one of the major protein antigens secreted from M. tuberculosis. Ag85B is thought to be a single immunogenic protein that can elicit a strong Th1-type immune response in hosts infected with mycobacteria, including individuals vaccinated with BCG. Administration of rAg85B showed a strong inhibitory effect on the development of allergic airway inflammation with induction of Th1-response and IL-17and IL-22 production. Both cytokines induced by rAg85B were involved in the induction of Th17-related cytokine-production innate immune cells in the lung. Administration of neutralizing antibodies to IL-17 or IL-22 in rAg85B-treated mice revealed that IL-17 induced the infiltration of neutrophils in BAL fluid and that allergen-induced bronchial eosinophilia was inhibited by IL-22. Furthermore, enhancement of the expression of genes associated with tissue homeostasis and wound healing was observed in bronchial tissues after rAg85B administration in a Th17-related cytokine dependent manner. The results of this study provide evidence for the potential usefulness of rAg85B as a novel approach for anti-allergic effect and tissue repair other than the role as a conventional TB vaccine.
authors.affiliation: Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Ibaraki, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Tsujimura
authors.affiliation: Department of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Mie, Japan.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Inada
authors.affiliation: Department of Pathologic Oncology, Institute of Molecular and Experimental Medicine, Faculty of Medicine, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Misao
authors.initials: M
authors.lastname: Yoneda
authors.affiliation: Research Laboratories, Kyoto R&D Center, Maruho Co., Ltd, Chudoji, Shimogyo-ku, Kyoto, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Fujita
authors.affiliation: Research and Development Department, Japan BCG Laboratory, Kiyose, Tokyo, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Laboratory of Immunoregulation and Vaccine Research, Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Ibaraki, Japan; Department of Immunoregulation, Mie University Graduate School of Medicine, Tsu, Mie, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yasutomi
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000008:administration & dosage* / Q000235:genetics* / Q000627:therapeutic use; D004195:Disease Models, Animal; D005260:Female; D007113:Immunity, Innate; D020381:Interleukin-17 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000009:adverse effects; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology*; D011994:Recombinant Proteins / Q000008:administration & dosage; D018417:Th1 Cells / Q000378:metabolism*; D000097043:Interleukin-22
chemical_list: D000942:Antigens, Bacterial; D020381:Interleukin-17; D007378:Interleukins; D010047:Ovalbumin; D011994:Recombinant Proteins; D000097043:Interleukin-22; C065036:antigen 85, Mycobacterium bovis