Immature Enterocytes Research Articles

Combined expression of pancreatic duodenal homeobox 1 and islet factor 1 induces immature enterocytes to produce insulin.

Immature rat intestinal stem cells (IEC-6) given the ability to express the transcription factor, pancreatic duodenal homeobox 1 (Pdx-1), yielded YK cells. Although these cells produced multiple enteroendocrine hormones, they did not produce insulin. Exposure of YK cells to 2 nmol/l betacellulin yielded BYK cells that showed the presence of insulin expression in cytoplasm and that secreted insulin into culture media. By examining the mechanism of differentiation in BYK cells, we found that another transcription factor, islet factor 1 (Isl-1) was newly expressed with the disappearance of Pax-6 expression in those cells after exposure to betacellulin. These results indicated that combined expression of Pdx-1 and Isl-1 in IEC-6 cells was required for the production of insulin. In fact, overexpression of both Pdx-1 and Isl-1 in IEC-6 cells (Isl-YK-12, -14, and -15 cells) gave them the ability to express insulin without exposure to betacellulin. Furthermore, implantation of the Isl-YK-14 cells into diabetic rats reduced the animals' plasma glucose levels; glucose levels dropped from 19.4 to 16.9 mmol/l 1 day after the injection of cells. As expected, the plasma insulin concentrations were 2.7 times higher in the diabetic rats injected with Isl-YK-14 cells compared to in controls. In summary, our results indicated that immature intestinal stem cells can differentiate into insulin-producing cells given the ability to express the transcription factors Pdx-1 and Isl-1.

Regulation of triacylglycerol and phospholipid trafficking by fatty acids in newborn swine enterocytes.

We (Wang H, Berschneider HM, Du J, and Black DD. Am J Physiol Gastrointest Liver Physiol 272: G935-G942, 1997; Wang H, Lu S, Du J, Yao Y, Berschneider HM, and Black DD. Am J Physiol Gastrointest Liver Physiol 280: G1137-G1144, 2001) previously showed that different fatty acids influence synthesis and secretion of triacylglycerol (TG) and phospholipid (PL) in a newborn swine enterocyte cell line (IPEC-1). The most striking effects were produced by stearic acid (SA; 18:0), which modestly affected TG and PL synthesis but reduced TG and PL secretion, and by eicosapentaenoic acid (EPA; 20:5), which reduced TG and PL synthesis and TG secretion relative to oleic acid (OA; 18:1). To define the mechanism of these effects, differentiated IPEC-1 cells were incubated for 24 h with OA, SA, or EPA and [(3)H]glycerol. Endoplasmic reticulum (ER) and Golgi (G) content of labeled lipids and apolipoprotein (apo) B and apoAI protein were measured. Relative to OA, SA did not impair ER TG synthesis, but reduced movement of labeled TG from ER to G. EPA impaired both ER TG synthesis and movement of labeled TG from ER to G. PL followed the same pattern, except ER synthesis of PL was relatively unaffected by EPA. Carbonate treatment demonstrated decreased partitioning of labeled lipid from ER membrane to lumen in EPA-treated cells. Organelle apoB and apoAI content demonstrated opposite patterns after SA and EPA incubation. We conclude that SA and EPA adversely influence immature enterocyte ER to G lipid trafficking, compared with OA. Furthermore, EPA inhibits ER lipid synthesis and transfer of membrane lipid to luminal particles. Regulation of apoAI ER to G trafficking is independent of that of apoB.

Small intestinal morphology in weaned piglets fed a diet containing spray-dried porcine plasma

The hypothesis tested in this study was that the reported beneficial effects of spray-dried porcine plasma (SDPP) on piglet post-weaning performance and health are associated with a trophic effect on small intestinal mucosa. At 24 days of age, the piglets of seven sows were assigned to one of three treatment groups. One group continued to be suckled. The other two groups were weaned and offered a diet containing either 15 per cent SDPP or casein. From each treatment group, one piglet was anaesthetised and samples were taken from the small intestinal wall at 26, 28 and 31 days of age. There were no significant effects of SDPP versus casein on villus length. On average, there was less mitotic activity in the SDPP -fed piglets than in those fed casein on days 4 and 7 after weaning. As less mitotic activity leads to less immature enterocytes, this may provide a mechanism for the reported beneficial effects of SDPP on performance and health.

The role of infection in necrotising enterocolitis

The role of infection in necrotising enterocolitis

Differentiation of immature enterocytes into enteroendocrine cells by Pdx1 overexpression.

The development of a variety of enteroendocrine cells of the gut is poorly understood. We tested whether immature intestinal stem cells were switched to multiple enteroendocrine hormone-producing cells by in vitro transfer of a homeobox gene. We transfected the pancreatic-duodenal homeobox 1 gene (Pdx1) into IEC-6 cells, an embryonic intestinal epithelial cell line derived from a normal rat, and selected the cells that overexpressed Pdx1 by 150-fold compared with control. The cells were examined for differentiation into enteroendocrine cells by immunocytochemical and electron microscopic analyses. Transfected cells cultured on micropore filters formed a trabecular network piled up on monolayer cells. These trabecular cells showed nuclear localization of Pdx1 protein and contained well-developed rough endoplasmic reticulum as well as many secretory granules of pleomorphic shape in the cytoplasm. Antibodies against chromogranin A, serotonin, cholecystokinin, gastrin, and somatostatin stained these secretory granules in the cytoplasm. Furthermore, immunofluorescence double staining analysis showed that different hormones were produced within a cell. These results provide the evidence that immature intestinal epithelial cells can differentiate into multiple hormone-producing enteroendocrine cells in response to overexpression of Pdx1.

Integrin Expression, Enterocyte Maturation, and Bacterial Internalization

Background. Little is known about the molecular mechanisms involved in the translocation of enteric bacteria. Adhesion molecules mediate interactions between some enteric pathogens and mammalian cells, but no such interactions have been identified for enterocytes and normal enteric bacteria. Using enteric pathogens, adhesion molecule expression has been linked to bacterial internalization and to enterocyte differentiation. Therefore, experiments were designed to study enterocyte integrin expression and differentiation, as well as enterocyte internalization of Salmonella typhimurium, Proteus mirabilis, and Escherichia coli.Materials and methods. Relative expression of the α2, α3, and β1 integrin subunits on Caco-2 and HT-29 enterocytes (mature and immature) was measured by ELISA. Bacteria-enterocyte surface interactions were observed by light and scanning electron microscopy. Bacterial internalization by enterocytes was quantified using the gentamicin protection assay.Results. Expression of the α2, α3, and β1 integrin subunits was consistently increased in immature compared to mature Caco-2 enterocytes; however, compared to mature enterocytes, immature HT-29 enterocytes had similar expression of α3 and β1 but decreased α2. Compared to untreated mature enterocytes, bacterial internalization was increased in immature enterocytes as well as mature enterocytes with lateral membranes artifactually exposed. However, there was no difference in bacterial internalization between immature enterocytes and mature enterocytes treated to expose the lateral membrane.Conclusions. Bacterial internalization by enterocytes appeared to be due to factors other than integrin expression or enterocyte differentiation. Exposure of the lateral enterocyte membrane may play an important role in facilitating bacterial internalization by enterocytes.

Primary murine small intestinal epithelial cells, maintained in long-term culture, are susceptible to rotavirus infection.

We describe a method for long-term culture of primary small intestinal epithelial cells (IEC) from suckling mice. IEC were digested from intestinal fragments as small intact units of epithelium (organoids) by using collagenase and dispase. IEC proliferated from organoids on a basement-membrane-coated culture surface and remained viable for 3 weeks. Cultured IEC had the morphologic and functional characteristics of immature enterocytes, notably sustained expression of cytokeratin and alkaline phosphatase. Few mesenchymal cells were present in the IEC cultures. IEC were also cultured from adult BALB/c mice and expressed major histocompatibility complex (MHC) class II antigens for at least 48 h in vitro. Primary IEC supported the growth of rhesus rotavirus (RRV) to a greater extent than a murine small intestinal cell line, m-IC(cl2). Cell-culture-adapted murine rotavirus strain EDIM infected primary IEC and m-IC(cl2) cells to a lesser extent than RRV. Wild-type EDIM did not infect either cell type. Long-term culture of primary murine small intestinal epithelial cells provides a method to study (i) virus-cell interactions, (ii) the capacity of IEC to act as antigen-presenting cells using a wide variety of MHC haplotypes, and (iii) IEC biology.

Inflammation in the developing human intestine: A possible pathophysiologic contribution to necrotizing enterocolitis.

Necrotizing enterocolitis (NEC), a major cause of morbidity and mortality in premature infants, occurs after the introduction of oral feedings in conjunction with initial bacterial colonization of the gut and is hypothesized to be due to an immature (inappropriate) enterocyte response to bacterial stimuli. To test this hypothesis, we compared the enterocyte IL-8 response to inflammatory stimuli [lipopolysaccharide (LPS) and IL-1beta] in immature vs. mature human small intestine. Initial in vitro studies comparing confluent Caco-2 cells, a model for mature human enterocytes, with a primary human fetal intestinal cell line (H4 cells) demonstrated that after inflammatory stimulation fetal cells secreted more IL-8 (LPS, 8-fold; IL-1beta, 20-fold) than Caco-2 cells. IL-8 mRNA activity in fetal compared to Caco-2 cells was proportionately increased by the same magnitude with both stimuli. To validate the in vitro observations, small intestinal organ cultures from fetuses vs. older children were exposed to LPS and IL-1beta. Again in human organ cultures from fetuses compared to older children, IL-8 secretion was greater (LPS, 2.5-fold; IL-1beta, 200-fold) and mRNA activity after stimulation was comparably higher, suggesting that increased transcription of the IL-8 gene may account for the excessive response. Using immunohistochemical staining to identify the cellular source of IL-8, activity was noted predominantly in villous and crypt epithelium but also in a few immunoresponsive lymphoid cells. The observation that immature human enterocytes react with excessive pro-inflammatory cytokine production after inflammatory stimulation may help in part explain why prematures exposed to initial colonizing bacteria develop necrotizing enterocolitis.

Role of Nutrients and Bacterial Colonization in the Development of Intestinal Host Defense

In this introduction to the supplement on the use of pre- and probiotics in the health and disease of pediatric patients, I have summarized factors affecting the initial colonization of the neonatal intestine. The term bacterial-epithelial cross-talk was defined, and examples of the enterocyte response to both pathologic and indigenous flora stimulation illustrated. Immaturities in the human neonatal intestinal response to bacteria and their toxins were reviewed in the context of the pathogenesis of age-specific, bacterial gastrointestinal infectious diseases. Finally, the importance of pre- and probiotics as measures to strengthen the neonate's intestinal host defenses in the prevention and treatment of specific age-related disease were considered.

The effect of mucin on bacterial translocation in I-407 fetal and Caco-2 adult enterocyte cultured cell lines.

Although the intestinal mucosa forms a crucial barrier between the host and the environment, bacterial translocation (BT) occurs frequently in neonates and may be a source of sepsis. The intestinal mucous gel layer is thought to be a vital component of the gut barrier and is composed, in part, of a family of glycoproteins known as mucins. Our aim was to study the effects of mucin on BT in an enterocyte cell-culture model using a fetal (I-407) and an adult (Caco-2) intestinal cell line. I-407 and Caco-2 cells were grown to confluence on porous filters in a two-chamber Transwell system. The integrity of the monolayers was confirmed by transepithelial electrical resistance (TEER) and permeability using the macromolecule dextran blue. Cells were treated with mucin (40 mg/ml) prior to inoculation of 1 x 10(6) Escherichia coli C25. The magnitude of BT was determined quantitatively by culturing the samples from the basal chamber of the wells and was expressed as log 10 [Colony Forming Units (CFU)/ml]. Statistical analysis was performed by the Mann-Whitney U test with statistical significance at P < 0.05. Mucin inhibited BT across both fetal and adult cultured enterocyte monolayers; however, the inhibitory effect was less on the fetal cells compared to the adult cells. Dextran-blue studies showed that monolayers were intact throughout the experiments. Despite 98% inhibition of BT, mucin had a statistically significant effect on post-bacterial inoculation TEER in Caco-2 cells and no effect in I-407 cells. The ability of mucin, a mucous-barrier glycoprotein, to inhibit BT across immature intestinal enterocytes, as in the neonate, may be diminished compared to mature adult enterocytes.

Iron regulatory protein as an endogenous sensor of iron in rat intestinal mucosa. Possible implications for the regulation of iron absorption.

Duodenal enterocytes adjust intestinal iron absorption to the body's state of iron repletion. Here we tested how iron supply from the blood modulates the RNA-binding activity of iron regulatory proteins (IRP-1 and IRP-2) in immature duodenal rat enterocytes, and whether the modulation is compatible with the hypothesis that IRPs, in turn, may regulate the expression of iron transport proteins in maturating enterocytes during migration to the villus tips. Tissue uptake of parenterally applied 59Fe along the duodenal crypt-villus axis was compared to local IRP-1 and IRP-2 activity and to duodenal 59Fe transport capacity 12 h, 48 h, and 72 h after intravenous iron administration to iron-deficient rats. IRP-1 and IRP-2 activity was significantly increased in iron-deficiency. 59Fe administrated from the blood side was almost exclusively taken up by crypt enterocytes. Accordingly, the activity of IRP-1 decreased at this site 12 h after parenteral iron administration, but remained high at the villus tips. After 48 h the bulk of 59Fe containing enterocytes had migrated to the villus tips. Correspondingly, IRP-1 activity was decreased at duodenal villus tips after 48 h. IRP-2 activity also tended to decrease, though the change was statistically not significant. IRP-2 activity remained significantly higher at duodenal villus tips than in crypts, even after 72 h. Intestinal iron absorption capacity decreased with the same delay as IRP-1 activity after intravenous iron administration. In the ileum 59Fe uptake from the blood and IRP activity showed no significant difference between crypt and villus region. Luminal administration of iron decreased duodenal IRP-1 and IRP-2 activity at tips and crypts within 2 h. Thus, recently absorbed iron becomes available to cytosolic IRP during its passage through the enterocyte. Our results are compatible with a role of IRPs in gearing the expression of intestinal iron transporters in the duodenal brushborder to the body's state of iron repletion.

Oral insulin is biologically active on rat immature enterocytes.

Oral insulin is biologically active on rat immature enterocytes.

Expression of insulin receptors and of 60-kDa receptor substrate in rat mature and immature enterocytes.

The mechanism(s) by which rat immature enterocytes exhibit increased responsiveness to insulin before weaning is unknown. Therefore, we have analyzed the distribution, ontogeny, and molecular properties of insulin receptors (IR) and of related substrates in immature and mature enterocytes. IR were studied by radioligand binding assays, cross-linking labeling, immunohistochemistry, and in vitro phosphorylated substrates by immunoprecipitation. Regardless of age, 125I-insulin binding to IR was five times higher in crypt cells than in villus cells and two times higher in the ileum than in the jejunum. Binding capacity to villus cells from sucklings (day 14) exceeded three times that of older animals (day 30 and day 60). Scatchard analysis of equilibrium binding data confirmed an age-related decrease in low- and high-affinity receptor classes without change in affinity constants. In concordance, both alpha- and beta-IR subunits were more abundant in immature than in mature membranes. In vitro, insulin elicited the phosphorylation of three membrane proteins (96, 60 and 42 kDa), whose signals were virtually inhibited by preincubating membranes with antireceptor monoclonal antibodies. By immunoprecipitation, the 60-kDa signal was rapidly detected as a tyrosine-phosphorylated protein, expressed in mature and immature membranes, and identified as a receptor substrate phosphorylated in vitro by the IR tyrosine kinase. In conclusion, 1) increased responsiveness of rat immature enterocytes to insulin could be related to high membrane concentrations of IR and 2) normal rat enterocytes express a 60-kDa phosphotyrosine protein identified as a direct substrate of the IR tyrosine kinase.

Development of hydrogen peroxide (H 2O 2)-generating oxidases in chick organs with special reference to kidneys

The developmental pattern of H2O2-producing oxidases (OX) was studied in chick kidneys (mesonephros, metanephros), intestine, liver, yolk sac and adrenal glands between embryonic days (ED) 5-20 as well as in chick organs after hatching. Sections from snap frozen tissue fixed in cold cacodylate-buffered 2% glutaraldehyde were processed by cerium-DAB-Co-H2O2 methods for benzylamine OX, diamine OX, histamine OX, alpha-hydroxyacid OX, D-amino acid OX (AAOX) and monoamine OX (MAOX). Prenatally, only activities of AAOX and MAOX could be demonstrated. AAOX appeared primarily in the proximal tubular cells of both types of kidneys. In the metanephros the enzyme was also detected in the thick ascending limbs of Henle's loops. The amount of reaction product in tubular cells increased with their maturation. MAOX activity was detected in immature enterocytes, in smooth muscle cells of large systemic arteries (on ED 5-6) as well as in proximal tubular cells of the mesonephros and adrenal gland. Later the enzyme appeared also in smooth muscle cells of the intestinal wall and in endothelial and smooth muscle cells of arterioles of the mesonephros. In the metanephros MAOX was detected at the same locations with a time delay because of a developmental shift of the kidney. Inhibition tests revealed that MAOX differs in epithelial cells from that in smooth muscle cells. Benzylamine OX, diamine OX and histamine OX were detected postnatally in smooth muscle cells of the arterial media and muscularis externa of the intestinal wall with low activities. It is concluded that MAOX and AAOX activities represent useful markers in the development of renal tubules. In addition, MAOX activity can be considered an indicator of maturation of components of the vascular wall.

Characterization of Myosin-IA and Myosin-IB, Two Unconventional Myosins Associated with theDrosophilaBrush Border Cytoskeleton

The expression patterns of myosin-IA (MIA) and myosin-IB (MIB), two novel unconventional myosins fromDrosophila melanogaster,have been characterized through immunoblot analysis and immunocytochemistry of embryos, larvae, and adults. The appearance and distribution of both proteins during embryogenesis is correlated with the formation of a brush border within the alimentary canal as documented at the ultrastructural level. MIA and MIB, both found predominantly at the basolateral domain of immature enterocytes, exhibit increased expression at the apical domain of differentiated enterocytes co-incident with microvillus assembly. Colocalization of MIA and MIB to larval and adult gut by confocal microscopy demonstrates distinct but overlapping subcellular distributions of these two proteins. In the larval brush border, MIA is enriched in the subapical terminal web domain whereas MIB is found predominantly in the apical microvillar domain. In the adult gut, MIA and MIB both exhibit a microvillar component as MIA attains a more apical position in addition to its previous terminal web locale. MIB is also found in egg chambers at both the basolateral and apical surfaces of the somatic follicle cells during oogenesis. MIA and MIB both demonstrate ATP-dependent extraction from the larval brush border cytoskeleton and exogenous F-actin, biochemical properties characteristic of functional myosins-I.

Lymphoid tissues of the ileum in young horses: distribution, structure, and epithelium.

Lymphoid tissues in the ileum of young horses form raised plaques that are macroscopically visible from the mucosal surface. These are termed "ileal lymphoid patches". These patches are variable in size, shape and position within the ileal wall, occasionally lying along the site of mesenteric attachment. Within lymphoid patches, follicles exist in three different morphological forms: follicle/dome structures, proprial follicles, and lymphoglandular complexes (LGCs). In follicle/dome structures, the majority of the follicle lies in the submucosa and merges with a dome in the lamina propria through a gap in the muscularis mucosae. In proprial follicles, the majority, or all, of the follicle is found in the lamina propria, and in LGCs, the follicles lie in the submucosa and communicate with the intestinal lumen via a central invagination of epithelium that extends vertically through a gap in the muscularis mucosae. Follicle-associated epithelium covers the follicle/dome structures and proprial follicles. It consists of enterocytes, cells morphologically resembling M cells, intraepithelial lymphocytes, goblet cells, and amine-precursor uptake and decarboxylation (APUD) cells. The epithelium of LGCs is mainly populated by immature enterocytes, intraepithelial lymphocytes and goblet cells. Cells with coarse, long microvilli are also present. Information regarding the presence of LGCs in the small intestine is scant, but LGCs have been well described in the large intestine of many species. Further investigation will be required to determine if factors exist that are common to both the ileum of the horse and the large intestine of other species to influence the development of LGCs at these specific sites.

Response of rat immature enterocytes to insulin: Regulation by receptor binding and endoluminal polyamine uptake

The mechanism(s) by which insulin stimulates enzyme expression in rat immature enterocytes are unknown. The purpose of this study was to investigate these mechanism(s). The effects of insulin or an antireceptor monoclonal antibody (RPN 538) were assessed on microvillous enzyme activities and the endoluminal uptake of [14C]spermine. Changes in de novo synthesis of polyamines were measured by mucosal ornithine decarboxylase activity. In sucklings (day 14), administration of insulin failed to induce intestinal ornithine decarboxylase activity, whereas in older rats (day 18 and 20), ornithine decarboxylase was enhanced by 2-2.5-fold. Immature enterocytes from sucklings, pretreated with alpha-difluoromethylornithine, remained sensitive to insulin and expressed enzyme activities at levels equal to controls. In response to insulin, the uptake of [14C]spermine and the mucosal concentrations of spermine and spermidine were increased by 30%, 13%, and 39%, respectively. Administration of RPN 538 had no effect on [14C]-spermine uptake, but it prevented the effects of endogenous insulin on enzyme expression. The enzymatic response of immature enterocytes to insulin is mediated by binding of the hormone to its receptor and is transduced into the cell without de novo synthesis of polyamines. The regulation by insulin of the endoluminal uptake of spermine could be critical for intestinal maturation.

Morphologic Characterization of Castor Oil-induced Colitis in Ponies

Ten ponies (160-250 kg, ages 17 months to 20 years) developed severe diarrhea within 24 hours of castor oil administration (2.5 ml/kg orally). The diarrhea was most severe between 24 and 48 hours post-dosing and subsided by 72 hours. Ponies were euthanatized at 24, 48, and 72 hours post-dosing and intestine was evaluated histologically and ultrastructurally. Twenty-four hours after dosing, the mucosa of the cecum and ventral colon had extensive superficial epithelial erosion and neutrophil infiltration. In the ileum, the epithelium of villous tips was separated from the lamina propria. Scanning electron microscopic examination of the cecal mucosa revealed that basement membranes were exposed in most areas except within necks of crypts. Ultrastructurally, changes in superficial enterocytes of the cecum and ventral colon were characterized by loss of microvilli, distortion of the cytoplasmic terminal web, expansion of the cytoplasmic matrix with formation of precipitates, and widening of intercellular spaces between junctional complexes. Enterocytes located within necks of crypts were flattened along the basement membrane and extended to margins of erosions. Venules within the superficial lamina propria were occluded by fibrin thrombi. Erosions in the cecum and ventral colon of ponies examined 48 hours after treatment were less extensive than those of ponies examined at 24 hours. At 48 hours post-dosing, basement membranes adjacent to crypts were covered by cuboidal enterocytes characterized ultrastructurally by sparse, irregularly shaped microvilli located on broad cytoplasmic protrusions and by numerous free ribosomes. These features indicated that immature enterocytes had migrated from crypts to resurface the eroded mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)

In VitroSystems for the Study of Cereal Proteins Toxic in Coeliac Disease

For a number of years, we have been carrying out investigations intended to clarify the nature of the toxic gliadin peptides, and whether different species and/or cultivars of wheat are tolerated to varying extents by people suffering from coeliac disease. Our investigations have been carried out using three main biological systems: 1) cultures of biopsy specimens of human intestinal mucosa; 2) cultures of rat fetal intestine; and 3) cultures of erythroid K562(S) cells.Using these systems, we have tested several peptide mixtures prepared from gliadin and non-gliadin fractions extracted from wheats having various degrees of ploidy and from other cereals. Fraction preparation has been carried out by means of sequential digestion with pepsin and trypsin under experimental conditions simulating protein digestion in man. The results obtained indicate that the pathological symptoms associated with intolerance to gluten are largely due to the cytotoxic activity of wheat gliadin peptides toward immature enterocytes.

Immunocytological responses in porcine proliferative enteropathies.

The ileum, colon, and mesenteric lymph nodes of pigs naturally affected by either of the two major forms of proliferative enteropathy, namely, intestinal adenomatosis or hemorrhagic enteropathy, were examined for immunocytological responses to infection by immunocytochemistry, using antibodies directed against elements of the porcine immune system. In both forms, there was mucosal proliferation of immature enterocytes which lacked substantial major histocompatibility complex class II expression and a marked accumulation of immunoglobulin A (IgA) at the apical cytoplasm of affected enterocytes in association with intracellular Campylobacter-like organisms. In intestinal adenomatosis, there was only a mild infiltration of CD8+ and CD25+ T cells in the intestinal lamina propria. In hemorrhagic enteropathy, there was a moderate infiltration of CD8+ and CD25+ T cells and IgM+ B cells in the lamina propria. In rats and humans, villous enterocytes are thought to act as antigen-presenting cells, with major histocompatibility complex class II molecules present on their surface, capable of initiating a T-cell response (particularly of CD8+ T cells) in response to bacterial antigens. Therefore, the selection of immature crypt cells by the intracellular Campylobacter-like organisms for entry and multiplication may represent a remarkable microbial adaptation associated with local immunomodulation and enhanced bacterial survival. The accumulation of IgA within affected enterocytes may represent a reduced capability of the cells to process nonspecific IgA or an accumulation of specific IgA.