Microbiota-stimulated immune mechanisms to maintain gut homeostasis

Chung, Hachung; Kasper, Dennis L.

doi:10.1016/j.coi.2010.06.008

Cited by 186 publications

(138 citation statements)

References 76 publications

(72 reference statements)

Supporting

Mentioning

127

Contrasting

Order By: Relevance

“…The direct ability of commensal bacteria to provoke epithelial ROS generation was initially surprising, but others reported similar data (21,32,44). Moreover, the interface between the commensal flora and the colonic epithelium is important for normal physiology (e.g., vitamin and short-chain fatty acid absorption) and host defense: commensal flora that gain access to the systemic circulation can be lifethreatening (1,10,12,13). Thus, ROS generation in response to commensal bacteria may be a means to regulate bacterial growth and may be important signaling molecules in the normal cross talk between the intestinal microbiota and the host.…”

Section: Discussionmentioning

confidence: 95%

“…The single layer of epithelial cells that line the gastrointestinal tract must keep the commensal microbiota at bay, which, despite providing many benefits for their host (10,12,13), are a source of danger signals and triggers of pathophysiological events (1). While controversy exists as to whether increases in epithelial permeability are a cause or a consequence of intestinal disease, there is little doubt that reduced epithelial integrity, whether due to frank ulceration or more subtle increases in paracellular or transcellular permeation, can promote inflammation (38).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Indomethacin-induced translocation of bacteria across enteric epithelia is reactive oxygen species-dependent and reduced by vitamin C

Schoultz

McKay

Graepel

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

Schoultz I, McKay CM, Graepel R, Phan VC, Wang A, Söderholm J, McKay DM. Indomethacin-induced translocation of bacteria across enteric epithelia is reactive oxygen species-dependent and reduced by vitamin C. Am J Physiol Gastrointest Liver Physiol 303: G536-G545, 2012. First published June 14, 2012 doi:10.1152/ajpgi.00125.2012.-The enteric epithelium must absorb nutrients and water and act as a barrier to the entry of luminal material into the body; this barrier function is a key component of innate immunity. Nonsteroidal anti-inflammatory drug (NSAID)-induced enteropathy occurs via inhibition of prostaglandin synthesis and perturbed epithelial mitochondrial activity. Here, the direct effect of NSAIDs [indomethacin, piroxicam (cyclooxygenase 1 and 2 inhibitors), and SC-560 (a cyclooxygenase 1 inhibitor)] on the barrier function of human T84 epithelial cell line monolayers was assessed by transepithelial electrical resistance (TER) and internalization and translocation of a commensal Escherichia coli. Exposure to E. coli in the presence and absence of drugs for 16 h reduced TER; however, monolayers cotreated with E. coli and indomethacin, but not piroxicam or SC-560, displayed significant increases in internalization and translocation of the bacteria. This was accompanied by increased reactive oxygen species (ROS) production, which was also increased in epithelia treated with E. coli only. Colocalization revealed upregulation of superoxide synthesis by mitochondria in epithelia treated with E. coli ϩ indomethacin. Addition of antioxidants (vitamin C or a green tea polyphenol, epigallocathechin gallate) quenched the ROS and prevented the increase in E. coli internalization and translocation evoked by indomethacin, but not the drop in TER. Evidence of increased apoptosis was not observed in this model. The data implicate epithelial-derived ROS in indomethacin-induced barrier dysfunction and show that a portion of the bacteria likely cross the epithelium via a transcellular pathway. We speculate that addition of antioxidants as dietary supplements to NSAID treatment regimens would reduce the magnitude of decreased barrier function, specifically the transepithelial passage of bacteria. permeability; nonsteroidal anti-inflammatory drug; mitochondria; intestine

show abstract

Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 99%

Indomethacin-induced translocation of bacteria across enteric epithelia is reactive oxygen species-dependent and reduced by vitamin C

Schoultz

McKay

Graepel

et al. 2012

American Journal of Physiology-Gastrointestinal and Liver Physi

View full text Add to dashboard Cite

show abstract

“…In mammals, a variety of secretory immunoproteins (e.g., IgA) and factors help shape gut microbial communities (23,24). A sim- Fig.…”

Section: Discussionmentioning

confidence: 99%

A role for variable region-containing chitin-binding proteins (VCBPs) in host gut–bacteria interactions

Dishaw

Giacomelli²,

Melillo³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

114

View full text Add to dashboard Cite

A number of different classes of molecules function as structural matrices for effecting innate and adaptive immunity. The most extensively characterized mediators of adaptive immunity are the immunoglobulins and T-cell antigen receptors found in jawed vertebrates. In both classes of molecules, unique receptor specificity is effected through somatic variation in the variable (V) structural domain. V region-containing chitin-binding proteins (VCBPs) consist of two tandem Ig V domains as well as a chitin-binding domain. VCBPs are encoded at four loci (i.e., VCBPA-VCBPD) in Ciona, a urochordate, and are expressed by distinct epithelial cells of the stomach and intestine, as well as by granular amoebocytes present in the lamina propria of the gut and in circulating blood. VCBPs are secreted into the gut lumen, and direct binding to bacterial surfaces can be detected by immunogold analysis. Affinity-purified native and recombinant VCBP-C, as well as a construct consisting only of the tandem V domains, enhance bacterial phagocytosis by granular amoebocytes in vitro. Various aspects of VCBP expression and function suggest an early origin for the key elements that are central to the dialogue between the immune system of the host and gut microflora.bacteria opsonization | bacteria phagocytosis | immunoglobulin variable domains D ifferent molecular and cellular mechanisms that effect "innate" or "adaptive" immune responses shape immunity to pathogens such as viruses, bacteria, and parasites in all metazoans. The innate immune system includes germline-encoded receptor molecules that recognize widely divergent molecular structures. In contrast, the gene loci that encode the receptor molecules of the adaptive immune system undergo unique rearrangements in individual somatic cells that expand clonally and account for nearlimitless functional variation of receptors. The adaptive immune response is limited to jawed vertebrate species, whereas innate immunity is characteristic of all metazoan phyla.Alternative mechanisms of innate and adaptive immunity have been described in jawless vertebrates, protochordates, and other invertebrates (1, 2). Given the absence of V domain-mediated immunity in jawless vertebrates, the protochordate lineages are particular significant for understanding the origins of V region diversity as a basic form of immune recognition. In the protochordate Branchiostoma floridae (amphioxus), variable region-containing chitin-binding proteins (VCBPs) were described that consist of two variable (V) Ig domains and a single chitin-binding domain (3). VCBPs are encoded by diverse, nonrecombining, haplotypically variable alleles (4-6). Detailed structural studies of VCBPs reveal that the hyperpolymorphic positions are localized on the β-sheet surfaces of the folded V domains (7) and not on the connecting loops, which are the sites of the highest variability in the V domains of Ig and T-cell receptor (TCR). Other innate immune functions (e.g., viral receptor and superantigen-binding sites) are associated with V regi...

show abstract

“…Under physiological conditions, the gut is covered by the largest epithelial surface in the body (around 200 m 2 in humans), and it contains complex and poorly understood cell interactions that regulate responses to food antigens and to antigens of the normal bacterial flora. [9][10][11][12][13][14][15] The barrier function of mucosal surfaces, particularly those of the intestine, is ensured by complex mechanisms acting on several levels. The microbiota itself forms an integral part of the natural mechanisms of mucosal surfaces and skin that safeguard the organism against pathogenic microorganisms.…”

Section: Introductionmentioning

confidence: 99%

The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases

et al. 2011

View full text Add to dashboard Cite

Microbiota-stimulated immune mechanisms to maintain gut homeostasis

Cited by 186 publications

References 76 publications

Indomethacin-induced translocation of bacteria across enteric epithelia is reactive oxygen species-dependent and reduced by vitamin C

Indomethacin-induced translocation of bacteria across enteric epithelia is reactive oxygen species-dependent and reduced by vitamin C

A role for variable region-containing chitin-binding proteins (VCBPs) in host gut–bacteria interactions

The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases

Contact Info

Product

Resources

About