The impact of perinatal immune development on mucosal homeostasis and chronic inflammation.

Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Philipps University Marburg, Medical Faculty, Baldingerstrasse, 35043 Marburg, Germany.
Nature Reviews Immunology (Impact Factor: 32.25). 12/2011; 12(1):9-23. DOI: 10.1038/nri3112
Source: PubMed

ABSTRACT The mucosal surfaces of the gut and airways have important barrier functions and regulate the induction of immunological tolerance. The rapidly increasing incidence of chronic inflammatory disorders of these surfaces, such as inflammatory bowel disease and asthma, indicates that the immune functions of these mucosae are becoming disrupted in humans. Recent data indicate that events in prenatal and neonatal life orchestrate mucosal homeostasis. Several environmental factors promote the perinatal programming of the immune system, including colonization of the gut and airways by commensal microorganisms. These complex microbial-host interactions operate in a delicate temporal and spatial manner and have an important role in the induction of homeostatic mechanisms.

1 Bookmark
  • [Show abstract] [Hide abstract]
    ABSTRACT: Eukaryotes rely on mitochondrial division to guarantee that each new generation of cells acquires an adequate number of mitochondria. Mitochondrial division has long been thought to occur by binary fission and, more recently, evidence has supported the idea that binary fission is mediated by dynamin-related protein (Drp1) and the endoplasmic reticulum. However, studies to date have depended on fluorescence microscopy and conventional electron microscopy. Here, we utilize whole cell cryo-electron tomography to visualize mitochondrial division in frozen hydrated intact HeLa cells. We observe a large number of relatively small mitochondria protruding from and connected to large mitochondria or mitochondrial networks. Therefore, this study provides evidence that mitochondria divide by budding.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aims: Storkhead Box 1 (STOX1) is a winged-helix transcription factor implicated in the genetic forms of a high-prevalence human gestational disease, preeclampsia. STOX1 overexpression confers preeclampsia-like transcriptomic features to trophoblastic cell lines, and preeclampsia symptoms to pregnant mice. The aim of this work was to evaluate the impact of STOX1 on free radical equilibrium and mitochondrial function, in vitro and in vivo. Results: Transcriptome analysis of STOX1-transgenic versus non-transgenic placentas at 16.5 days of gestation revealed alterations of mitochondria-related pathways. Placentas overexpressing STOX1 displayed altered mitochondrial mass and were severely biased towards protein nitration, indicating nitroso-redox imbalance in vivo. Trophoblast cells overexpressing STOX1 displayed an increased mitochondrial activity at 20% O2 and in hypoxia, despite a reduction of the mitochondrial mass in this situation. STOX1 overexpression is therefore associated to hyperactive mitochondria leading to increased free radical production. Moreover, nitric oxide (NO) production pathways were activated, resulting in peroxynitrite formation. At low oxygen pressure, STOX1 overexpression in the placenta as well as in a trophoblast cell line, switched the free radical balance from Reactive Oxygen Species (ROS) to Reactive Nitrogen Species (RNS). Innovation: In preeclamptic placentas, NO interacts with ROS to generate peroxynitrite and nitrated proteins as end products. This process will deprive the maternal organism of NO, a crucial vasodilator molecule. Conclusion: Our data posit STOX1 as a genetic switch in the ROS/RNS balance and suggest an explanation for elevated blood pressure in preeclampsia.
    Antioxidants & Redox Signaling 04/2014; · 8.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Secretory IgA (SIgA) antibodies in the intestinal tract form the first line of antigen-specific immune defense, preventing access of pathogens as well as commensal microbes to the body proper. SIgA is transported into external secretions by the polymeric immunoglobulin receptor (pIgR). Evidence is reported here that the gut microbiota regulates production of SIgA and pIgR, which act together to regulate the composition and activity of the microbiota. SIgA in the intestinal mucus layer helps to maintain spatial segregation between the microbiota and the epithelial surface without compromising the metabolic activity of the microbes. Products shed by members of the microbial community promote production of SIgA and pIgR by activating pattern recognition receptors on host epithelial and immune cells. Maternal SIgA in breast milk provides protection to newborn mammals until the developing intestinal immune system begins to produce its own SIgA. Disruption of the SIgA-pIgR-microbial triad can increase the risk of infectious, allergic and inflammatory diseases of the intestine.
    Immunology letters. 05/2014;