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.2015 Jul 4;6(4):279-83.
doi: 10.1080/19490976.2015.1060390. Epub 2015 Jun 11.

Proneness of TLR5 deficient mice to develop colitis is microbiota dependent

Affiliations

Proneness of TLR5 deficient mice to develop colitis is microbiota dependent

Vishal Singh et al. Gut Microbes..

Abstract

Alterations in the gut microbiota have been implicated to play a role in potentiating inflammatory bowel diseases in both humans and mice. Mice lacking the flagellin receptor, toll-like receptor 5 (TLR5), are prone to develop spontaneous gut inflammation, but are significantly protected when treated with antibiotics or maintained in germ-free conditions. However, given that the incidence of spontaneous inflammation in TLR5KO mice is quite variable in conventional conditions (typically ∼10% show clear colitis), this result is far from definitive and does not rule out that TLR5KO mice might be prone to develop inflammation even in the absence of a microbiota. Herein, we demonstrate that neutralization of IL10 signaling induces colitis in 100% of TLR5KO mice which provide a more rigorous approach to evaluate the role of microbiota in gut inflammation. Mice treated with antibiotics or maintained in germ-free condition are substantially protected against IL-10R neutralization-induced colitis, underscoring that gut inflammation in TLR5KO mice is dependent upon the presence of a gut microbiota.

Keywords: Abx; Germ-free mice; Gut bacteria; Interleukin-10; Intestinal inflammation; Toll-like receptor; antibiotics; GF; germ-free; IL-10; interleukin 10; MPO; myeloperoxidase..

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Figures

Figure 1.
Figure 1.
Gut sterilization prevents development of colitis in TLR5KO mice receiving α-IL-10R mAb. Age matched male TLR5KO mice (n = 5 ) with or without α-IL-10R mAb were treated with broad antibiotics (ampicillin and neomycin) in drinking water for 4 weeks and then analyzed for development of colitis. (A) Image displays gross pictures of colon. Bar graphs represent: Weights of (B) Ceca, (C) Colon, (D) Spleen, (E) MPO in colonic tissue, and (F) Serum Lcn2. Results are expressed, as mean ± SEM. Image is representative of 2 independent experiments. *p <0.05.
Figure 2.
Figure 2.
IL-10R neutralization failed to induce colitis in GF-TLR5KO mice. Age matched male GF-TLR5KO mice (n = 4−5) received α-IL-10R mAb (1.0 mg/mouse, i.p. weekly) up to 4 weeks and then analyzed for development of colitis. (A) Image displays gross picture of colon. Bar graphs represent: Weights of (B) Ceca, (C) Colon, (D) Spleen, (E) MPO in colonic tissue, and (F) Serum Lcn2. Results are expressed, as mean ± SEM.
See this image and copyright information in PMC

References

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