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. 2016 Aug;64(8):470-82.
doi: 10.1369/0022155416656154. Epub 2016 Jul 1.

The Expression of Toll-like Receptors in Normal Human and Murine Gastrointestinal Organs and the Effect of Microbiome and Cancer

Heikki Huhta  1   2   3   4 , Olli Helminen  1   2   3   4 , Joonas H Kauppila  1   2   3   4 , Tuula Salo  5   3   4 , Katja Porvari  1 , Juha Saarnio  2   3   4 , Petri P Lehenkari  2   6   3   4 , Tuomo J Karttunen  1   3   4
Affiliations

The Expression of Toll-like Receptors in Normal Human and Murine Gastrointestinal Organs and the Effect of Microbiome and Cancer

Heikki Huhta et al. J Histochem Cytochem. 2016 Aug.

Abstract

Toll-like receptors (TLRs) are innate immune receptors expressed in all parts of the alimentary tract. However, analyses comparing expression in different segments and data on germ-free animals are lacking. Alimentary tract cancers show increased TLR expression. According to the field effect concept, carcinogenetic factors induce subtle cancer predisposing alterations in the whole organ. We studied TLR1 to TLR9 expression in all segments of the alimentary tract from cancer patients' tumor-adjacent normal mucosa, healthy organ donors, and conventional and germ-free mice by using immunohistochemistry and quantitative PCR. All TLRs were expressed in all segments of the alimentary tract. Expression was most intensive in the small intestine in humans and conventional mice, but germ-free mice showed less expression in the small intestine. TLR expression levels were similar in cancer patients and organ donors. We provide systematic baseline data on the TLR expression in the alimentary tract. Normal epithelium adjacent to tumor seems to have similar TLR expression compared with healthy tissues suggesting absence of any field effect in TLR expression. Accordingly, specimens from cancer patients' normal tumor-adjacent tissue can be used as control tissues in immunohistochemical TLR studies in gastrointestinal cancer.

Keywords: Toll-like receptor; alimentary tract; cancer; expression; germ-free mouse; mouse; organ donor; tumor-adjacent normal epithelium.

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Conflict of interest statement

Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Histograms of Toll-like receptor (TLR) 1 to 9 histoscores from different anatomic segments of the alimentary tract in humans and in conventional and germ-free mouse.
Figure 2.
Figure 2.
Typical Toll-like receptor (TLR) expression patterns from the human ascending colon. TLRs are expressed throughout the epithelium with a diffuse manner. Paired figures from ascending colon organ donor (left) and tumor-adjacent normal epithelium (right) are presented: (A) TLR1, (B) TLR2, (C) TLR3, (D) TLR4, (E) TLR5, (F) TLR6, (G) TLR7, (H) TLR8, and (I) TLR9. 20× magnification was used and 50-µm scale bar is in panel I.
Figure 3.
Figure 3.
Typical Toll-like receptor (TLR) expression patterns from the conventional and germ-free mouse small intestines. TLRs are expressed throughout the epithelium with a diffuse manner. Paired figures from small intestine conventional (left) and germ-free mice (right) are presented: (A) TLR1, (B) TLR2, (C) TLR3, (D) TLR4, (E) TLR5, (F) TLR6, (G) TLR7, (H) TLR8, and (I) TLR9. 10× magnification was used and 50-µm scale bar is in panel I.
See this image and copyright information in PMC

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