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Medzhitov/Elsevier
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$ G* b* K+ A# B/ y! v2 S9 \Bugs that live in our gut are not only not harmful but provide signals that maintain gut tissue integrity, according to Seth Rakoff-Nahoum, Ruslan Medzhitov, and colleagues (Yale University, New Haven, CT).1 o) F- M+ q0 m8 T
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The benefits of commensal, or nonpathogenic gut bacteria, are well known. For example, these bacteria digest tricky carbohydrates and supply certain micronutrients. But inappropriately enthusiastic responses to the bacteria are characteristic of inflammatory bowel diseases (IBD) such as Crohn's disease. So Medzhitov suspected that mice less able to respond to bacterial products might end up better off.2 P: }" B+ h# \7 Q( ^
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Instead, mice deficient for Toll-like receptor (TLR) responses to bacterial products such as lipopolysaccharide (LPS) were more susceptible than wild-type mice to a colon-damaging chemical. The increased damage and death was not the result of bacterial invasion, as lymphocyte infiltration was low, and epithelial damage and bleeding remained high when the same mice had antibiotics added to their regimen. Furthermore, wild-type mice died from chemical-induced damage when treated with antibiotics that completely eliminated commensal bugs.# S4 g. L% X& Y2 n D g3 ~+ y
: h! J6 q* ~" T8 y! G0 n. B) ZLow doses of LPS or another TLR ligand rescued intestinal damage in the antibiotic-treated wild-type mice, apparently by inducing protective cytokines and heat shock proteins. Such a regimen might be contemplated for the damaged digestive tracts of chemotherapy patients, who are given high doses of prophylactic antibiotics to back up their weakened immune systems.6 I6 Z7 c- i" y }: \
5 e( U1 K0 d% mIn contrast to earlier conclusions by IBD researchers, Medzhitov says it is now clear that "the recognition of commensals is not just an unwanted side effect." The body may use the influx of commensals into an intestinal wound as an indicator of damage. In internal organs lacking commensals, there appear to be endogenous ligands that signal similarly, and indeed Medzhitov has preliminary evidence that some of these also induce the TLR system. Whether a tissue repair system evolved to take on an immune defense duty, or vice versa, is now open to debate.
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Rakoff-Nahoum, S., et al. 2004. Cell. 118:229–241.(A colon without commensals (bottom) cann) |
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发表于 2009-3-6 08:20
发表于 2015-5-27 20:48
