Cell host & microbe
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Cell host & microbe · Jul 2011
Foxp3(+) regulatory T cell expansion required for sustaining pregnancy compromises host defense against prenatal bacterial pathogens.
Although pregnancy confers unique susceptibility to infection, the pregnancy-associated immune defects that erode host defense remain largely undefined. Herein, we demonstrate that expansion of immune-suppressive Foxp3(+) regulatory T cells (Tregs) which occurs physiologically during pregnancy or when experimentally induced in transgenic mice caused enhanced susceptibility to prenatal pathogens including Listeria and Salmonella species. ⋯ Interestingly, Foxp3 cell-intrinsic defects in the immune-suppressive cytokine IL-10 alone were sufficient to override Treg-mediated infection susceptibility, while IL-10 was nonessential for sustaining pregnancy. Thus, maternal Treg expansion required for sustaining pregnancy creates naturally occurring holes in host defense that confer prenatal infection susceptibility.
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The dwindling supply of effective treatments for infectious disease is cause for alarm. Searches for anti-infectives yielding fewer and fewer novel discoveries have been concentrated in overly restricted regions of target space, screening space, chemical space, and competition space. Appreciating the diverse axes of these spaces may encourage wider exploration.
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Eicosanoids can have either proinflammatory effects or anti-inflammatory effects. Tobin and colleagues use a forward genetic screen in zebrafish to identify a key eicosanoid enzyme, leukotriene A(4) hydrolase (LTA(4)H), that controls susceptibility to mycobacterial infection. They also demonstrate that polymorphisms in LTA(4)H are associated with susceptibility to mycobacteria in humans.
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Cell host & microbe · May 2009
Comment Letter Multicenter StudyDuffy antigen polymorphisms do not alter progression of HIV in African Americans in the MACS cohort.
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Cell host & microbe · May 2009
Bone morphogenetic protein 4 signaling regulates epithelial renewal in the urinary tract in response to uropathogenic infection.
The transitional epithelium of the bladder normally turns over slowly but upon injury undergoes rapid regeneration fueled by basal uroepithelial stem and/or early progenitor cells (USCs). Little is known about the mechanisms underlying the injury response. We investigate the mechanism of bladder epithelial regeneration in response to infection with uropathogenic E. coli (UPEC). ⋯ In mice with induced urothelial ablation of a member of the TGF-beta receptor superfamily, bone morphogenetic protein (Bmp)-4 receptor, infection led to aberrant urothelial renewal resulting from a block in USC differentiation into superficial cells. Chemical injury also caused sloughing but no inflammation or USC activation. Together, our study indicates that UPEC infection but not chemical injury activates the USC niche, and Bmp signaling is required for regulation of the USC response to infection.