Lipopolysaccharide induces CD25-positive, IL-10-producing lymphocytes without secretion of proinflammatory cytokines in the human colon: low MD-2 mRNA expression in colonic macrophages.
Despite the huge number of colonized Gram-negative bacteria in the colon, the normal colon maintains its homeostasis without any excessive immune response. To investigate the potential mechanisms involved, human colonic lamina propria mononuclear cells (LPMCs) obtained from uninflamed mucosa were cultured with lipopolysaccharide (LPS) prepared from Bacteroides vulgatus (BV-LPS) or Bacteroides fragilis (BF-LPS), as representatives of indigenous flora, or pathogenic Salmonella minnesota (SM-LPS). Colonic LPMCs failed to produce inflammatory cytokines in response to any type of LPS. Colonic macrophages barely expressed mRNA for MD-2, an essential association molecule for LPS signaling via Toll-like receptor 4. Further, BV-LPS induced CD25 and Foxp3 expression in lymphocytes and CD4(+)CD25(+) cells expressed IL-10 mRNA. Thus, the low expression of functioning LPS receptor molecules and induction of IL-10-producing CD4(+)CD25(+) lymphocytes by indigenous LPS may play a central role in the maintenance of colonic immunological homeostasis.
Department of Gastroenterology, Research Institute, International Medical Center of Japan, 1-21-1 Toyama, Shinjuku-ku, Tokyo 162-8655, Japan.
Yuko
Y
Shirai
Masahito
M
Hashimoto
Rie
R
Kato
Yuki I
YI
Kawamura
Teruo
T
Kirikae
Hideaki
H
Yano
Junya
J
Takashima
Yujiro
Y
Kirihara
Yukio
Y
Saito
Masayuki A
MA
Fujino
Taeko
T
Dohi
D000368:Aged; D015703:Antigens, CD / Q000276:immunology; D015214:Antigens, Differentiation, Myelomonocytic / Q000276:immunology; D000954:Antigens, Surface / Q000235:genetics / Q000378:metabolism*; D001441:Bacteroides fragilis / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D003106:Colon / Q000276:immunology / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D006801:Humans; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology / Q000378:metabolism*; D051218:Lymphocyte Antigen 96; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000378:metabolism; D012475:Salmonella / Q000276:immunology / Q000378:metabolism; D063268:Sialic Acid Binding Ig-like Lectin 3
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000954:Antigens, Surface; C571163:CD33 protein, human; D016207:Cytokines; C495377:LY96 protein, human; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D063268:Sialic Acid Binding Ig-like Lectin 3; D016753:Interleukin-10