Toll-like receptor 4 mediates an antitumor host response induced by Salmonella choleraesuis

Che Hsin Lee, Chao Liang Wu, Ai Li Shiau

研究成果: Article同行評審

66 引文 斯高帕斯(Scopus)

摘要

Purpose: We have shown tumor-targeting and antitumor activities of an attenuated Salmonella choleraesuis in various tumor models. Meanwhile, host factors, including innate and adaptive immune responses, play roles in Salmonella-induced antitumor activity. Toll-like receptor 4 (TLR4) is identified as a signaling receptor for lipopolysaccharide derived from Gram-negative bacteria. However, the detailed mechanism of the S. choleraesuis - induced antitumor immune response via TLR4 remained uncertain. Experimental Design: Herein, we used wild-type C3H/HeN mice and TLR4-deficient C3H/HeJ mice to study the role of TLR4 in the antitumor immune responses induced by S. choleraesuis. Results: The amounts of S. choleraesuis were cleared more rapidly from the normal organs in C3H/HeN mice than those in C3H/HeJ mice. Tumors in C3H/HeN mice treated with S. choleraesuis were significantly smaller than those treated with PBS. By contrast, in TLR4-deficient mice, there was a slight difference in inhibition of tumor growth. Meanwhile, we found that S. choleraesuis significantly up-regulated IFN-γ, IFN-inducible chemokines CXCL9 (MIG), and CXCL10 (IP-10) productions in C3H/HeN mice, but not in C3H/HeJ mice. Furthermore, immunohistochemical staining of the tumors revealed less intratumoral microvessel density, more infiltration of macrophages, neutrophils, CD4+ and CD8+ T cells, and cell death in C3H/HeN mice after S. choleraesuis treatment compared with those in C3H/HeJ mice. The interaction between TLR4 and S. choleraesuis seemed to polarize the T-cell response to a T helper 1 - dominant state. Conclusions: These results suggest TLR4 may play an important role in the molecular mechanism of S. choleraesuis - induced host antitumor responses.

原文English
頁(從 - 到)1905-1912
頁數8
期刊Clinical Cancer Research
14
發行號6
DOIs
出版狀態Published - 2008 3月 15

All Science Journal Classification (ASJC) codes

  • 腫瘤科
  • 癌症研究

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