Enteric defensins are essential regulators of intestinal microbial ecology

Nita H Salzman, et al. 2010. Nat Immunol. 11, 76-82

Speaker: Miao-Hsi Hsieh (謝妙禧)                               Time: 15:10~16:00, Nov. 10, 2010

Commentator: Dr. Jyh-Wei Shin (辛致煒老師)           Place: Room 601

Abstract:

There are many microorganisms present in the mammalian intestine, and they maintain the symbiotic relationship with hosts. Although the colonization of these microbes could protect host intestinal mucosa system from infections, but the hosts still have other protect mechanism to prevent external microbial infections, such as the secretion of a-defensins from paneth cells to achieve anti-microbal function. (1) To determine if α-defensins also govern intestinal microbial ecology, this study apply two different strains of mice, one was the DEFA5-transgenic mice, in which paneth celloverexpressed a-defensins, and the other one, MMP7-deficient mice which lack of MMP7 enzyme to activate paneth cell in secretion of a-defensins, as the model of a-defensins deficient. First, from the comparision of the small intestinal flora between the DEFA5-transgenic mice and MMP7-deficient mice, the authors found that the existence of a-defensins could changed the flora in small intestine, but the total number of microbes in the small intestine did not change. The DEFA5-transgenic mice had higher Firmicutes and lower bacteria in the small intestine, while MMP7-deficient mice had opposite results as compared to DEFA5-transgenic mice. Second, they used FISH to detect the segment filamentous bacteria (SFB) in the small intestine of these two strains of mice They found that DEFA5-expressing mice had striking losses of SFB, and the wild type of offspring of DEFA5-transgenic mice (+/-) did not detect SFB. The abundant existences of SFB affect the number of CD4⁺IL-17A⁺ T cells in the lamina propria, therefore fewer interleukin 17 (IL-17)-producing lamina propria T cells was found in DEFA5-transgenic mice as compared to MMP7-deficient mice. Overall the study shows that the role of a-defensins is to regulate the makeup of the microbiota in the small intestine.

References:

1.Macpherson, A.J. & Harris, N.L. Interactions between commensal intestinal bacteria and the immune system. Nat. Rev. Immunol. 4, 478–485 (2004).