A human colonic commensal promotes colon tumorigenesis via activation of T helper type 17 T cell responses

Shaoguang Wu., et al. 2009. Nat. Med. 15, 1016-1022

Speaker: Ting-Jing Shen (沈庭靚)                         Time: 14:10~15:00, Dec. 30, 2009

Commentator: Dr. Huan-Yao Lei (黎煥耀博士)          Place: Room 601

Abstract:

Infection-induced inflammation is associated with cancer. Enterotoxigenic Bacteroides fragilis (ETBF) is a common human colonic commensal bacterium. It causes acute inflammatory diarrheal disease but also asymptomatically colonizes up to 20%–35% of adults globally. Recently, ETBF are shown to have potential to cause colon cancer (1). In this report, they compared multiple intestinal neoplasia (Min) mice inoculated with ETBF or nontoxigenic B. fragilis (NTBF) and found that the ETBF-colonized Min mice presented colonic inflammation and enhanced tumor formation.Furthermore, ETBF induced the activation of signal transducer and activator of transcription-3 (Stat3) in colonized Min mice with a selective increase of T helper type 17 (Th17) response whereas the inoculation of NTBF failed to induce either colitis or Stat activation. During infection, inflammatory cytokines help immune cell activation, such as stimulating the differentiation of effecter T cells into Th17 cells by interleukin-23 (IL-23) (2). Using antibodies to block the cytokine, they found that antibodies to IL-17A and IL-23R, but not to IFN-g, inhibited colon tumors on ETBF-colonized Min mice. Among the IL-17 producing cells, only CD4⁺ T cell was involved in enhancing the tumor number. Therefore, they provide new evidence about the connection of inflammation-induced tumorigenesis between common human colonic commensal bacterium and Th17 response.

References:

1.      Toprak, N.U., et al. 2006. A possible role of Bacteroides fragilis enterotoxin in the aetiology of colorectal cancer. Clin. Microbiol. Infect. 12, 782–786.

2.      Weaver, C.T., et al. 2007. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu. Rev. Immunol. 25, 821–852.