Human Th1 differentiation induced by lipoarabinomannan/lipomannan from Mycobacterium bovis BCG Tokyo-172.
Mycobacterium tuberculosis (tubercle bacilli) and the related acid-fast bacteria including Mycobacterium bovis Bacille Calmett-Guerin (BCG) have a characteristic cell wall (CW) containing various lipoglycans and glycolipids. Such lipoglycans have been reported to activate type-I inflammatory responses via dendritic cells (DCs) through Toll-like receptor 2. In this study, lipoglycans, lipoarabinomannan (LAM), lipomannan (LM) and phosphatidylinositol mannoside (PIM), were purified from the CW fractions of M. bovis BCG Tokyo-172, and the effect on the differentiation of human peripheral blood naive CD4 T cells into T(h)1 and T(h)2 was examined. LAM/LM molecules enhanced T(h)1 differentiation under both T(h)1 and T(h)2 conditions, whereas some other glycolipids and phospholipid enhanced T(h)2 differentiation under T(h)2 conditions. Other components had little effect under the given conditions. Even in highly purified CD4 T cell cultures, LAM/LM enhanced T(h)1 generation only under T(h)1 culture conditions. These results indicate that LAM/LM possesses a potent augmenting activity in T(h)1 differentiation in human CD4 T cells. LAM/LM appeared to act directly on naive CD4 T cells to enhance T(h)1 differentiation under T(h)1 culture conditions, while acting indirectly to up-regulate the generation of T(h)1 cells via IL-12/DCs under T(h)1 and T(h)2 conditions. Therefore, these results provide the first evidence indicating that LAM/LM from M. bovis BCG may possess a potent modulating activity in the human system, and thus supporting the strategy for the use of BCG components in the vaccine development for such T(h)2 diseases as allergic asthma and rhinitis.
Ito
Toshihiro
T
Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Hasegawa
Akihiro
A
Hosokawa
Hiroyuki
H
Yamashita
Masakatsu
M
Motohashi
Shinichiro
S
Naka
Takashi
T
Okamoto
Yuko
Y
Fujita
Yukiko
Y
Ishii
Yasuyuki
Y
Taniguchi
Masaru
M
Yano
Ikuya
I
Nakayama
Toshinori
T
D017951:Antigen Presentation / Q000187:drug effects; D000942:Antigens, Bacterial / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007111:Immunity, Cellular / Q000187:drug effects; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D009163:Mycobacterium bovis; D010716:Phosphatidylinositols / Q000276:immunology / Q000494:pharmacology; D018417:Th1 Cells / Q000166:cytology* / Q000276:immunology
D000942:Antigens, Bacterial; D008070:Lipopolysaccharides; D010716:Phosphatidylinositols; C050016:lipoarabinomannan; C064351:lipomannan; C034154:phosphatidylinositol mannoside