Gas6 ameliorates intestinal mucosal immunosenescence to prevent the translocation of a gut pathobiont, Klebsiella pneumoniae, to the liver.

Immunosenescence refers to the development of weakened and/or dysfunctional immune responses associated with aging. Several commensal bacteria can be pathogenic in immunosuppressed individuals. Although Klebsiella pneumoniae is a commensal bacterium that colonizes human mucosal surfaces, the gastrointestinal tract, and the oropharynx, it can cause serious infectious diseases, such as pneumonia, urinary tract infections, and liver abscesses, primarily in elderly patients. However, the reason why K. pneumoniae is a more prevalent cause of infection in the elderly population remains unclear. This study aimed to determine how the host's intestinal immune response to K. pneumoniae varies with age. To this end, the study analyzed an in vivo K. pneumoniae infection model using aged mice, as well as an in vitro K. pneumoniae infection model using a Transwell insert co-culture system comprising epithelial cells and macrophages. In this study, we demonstrate that growth arrest-specific 6 (Gas6), released by intestinal macrophages that recognize K. pneumoniae, inhibits bacterial translocation from the gastrointestinal tract by enhancing tight-junction barriers in the intestinal epithelium. However, in aging mice, Gas6 was hardly secreted under K. pneumoniae infection due to decreasing intestinal mucosal macrophages; therefore, K. pneumoniae can easily invade the intestinal epithelium and subsequently translocate to the liver. Moreover, the administration of Gas6 recombinant protein to elderly mice prevented the translocation of K. pneumoniae from the gastrointestinal tract and significantly prolonged their survival. From these findings, we conclude that the age-related decrease in Gas6 secretion in the intestinal mucosa is the reason why K. pneumoniae can be pathogenic in the elderly, thereby indicating that Gas6 could be effective in protecting the elderly against infectious diseases caused by gut pathogens.

Excited State Engineering in Ag29 Nanocluster through Peripheral Modification with Silver(I) Complexes for Bright Near-Infrared Photoluminescence.

The optical property of an ionic metal nanocluster (NC) is affected by the ionic interaction with counter ions. Here, we report that the modification of trianionic [Ag29(BDT)12(TPP)4]3- NC (BDT: 1.3-benzenedithiol; TPP: triphenylphosphine) with silver(I) complexes led to the intense photoluminescence (PL) in the near-infrared (NIR) region. The binding of silver(I) complexes to the peripheral region of Ag29 NC is confirmed by the single-crystal X-ray diffraction (SCXRD) measurement, which is further supported by electrospray ionization mass spectrometry (ESI-MS) and nuclear magnetic resonance (NMR) spectroscopy. The change of excited-state dynamics by the binding of silver(I) complexes is discussed based on the results of a transient absorption study as well as temperature-dependent PL spectra and PL lifetime measurements. The modification of Ag29 NCs with cationic silver(I) complexes is considered to give rise to a triplet excited state responsible for the intense NIR PL. These findings also afford important insights into the origin of the PL mechanism as well as the possible light-driven motion in Ag29-based NCs.

Selective Crystallization of Linkage Isomers, [RhIII(NCS)(SCN)5]3- and [RhIII(SCN)6]3-, to Investigate Structural Trans Influence and Thermal Stability.

Linkage isomers of homoleptic complexes, [RhIII(SCN)6]3- and [RhIII(NCS)(SCN)5]3-, formed in aqueous solution were successfully separated by employing methyltriphenylphosphonium (MePPh3+) and 1-ethylquinolinium (EtQu+) ions as countercations, respectively. The single-crystal X-ray analysis of (MePPh3)3[RhIII(SCN)6] (1) indicated that all of the SCN- ligands coordinate to the RhIII ion by S atoms with an octahedral symmetry, where the average bond length of Rh-S is 2.374(7) Å. On the other hand, the RhIII ion of (EtQu)3[RhIII(NCS)(SCN)5]·H2O (2) is coordinated by five S atoms and one N atom of the SCN- ligands with a C4v symmetry. Structural trans influence was observed in the shorter bond length of Rh-S at the trans position of Rh-N. The Rh-S bond length is 2.3398(13) Å significantly shorter than those of 1 by ca. 0.04 Å, although DFT calculations based on the crystal structures indicated that the effective bond order of Rh-N is higher than those of Rh-S. Thermal stability examination by thermogravimetric and differential thermal analyses (TG/DTA) and IR spectroscopy indicated that the linkage isomerization of [RhIII(SCN)6]3- to [RhIII(NCS)(SCN)5]3- proceeded after melting around 174 °C. These results clearly indicate that [RhIII(NCS)(SCN)5]3- is thermodynamically more stable than [RhIII(SCN)6]3- in solid states, although further linkage isomerization hardly occurs.

Long-term safety and efficacy of belimumab in Japanese patients with SLE: A 7-year open-label continuation study.

OBJECTIVES: Evaluate long-term safety, tolerability, and efficacy of belimumab in Japanese patients with systemic lupus erythematosus (SLE). METHODS: This was a subgroup analysis of Japanese patients who completed studies BEL113750 or BEL112341 and were enrolled in a Phase 3, open-label extension study (BEL114333; NCT01597622). Eligible patients received intravenous belimumab 10 mg/kg every 28 days for ≤7 years. Primary endpoint: safety and tolerability. Secondary endpoints included SLE Responder Index (SRI)-4 response rate, SRI-4 components, severe SLE flare, and use of corticosteroids/other SLE-related treatments. Analyses were based on observed data from first belimumab dose received in either parent or current study through to study end. RESULTS: Of 71 Japanese patients enrolled, 69.0% completed the study. Overall, 98.6% patients had adverse events (AEs); 32.4% had serious AEs. The proportion of SRI-4 responders increased progressively (Year 1, Week 24: 40.9% [27/66]; Year 7, Week 48: 84.6% [11/13]) as did the proportion of Safety of Estrogens in Lupus Erythematosus National Assessment-SLE Disease Activity Index responders. The proportion of patients with no worsening in PGA (91.2-100.0%) and no new organ damage (92.6-100.0%) remained stable over time. Severe SLE flare was experienced by 11.3% (8/71) of patients. Corticosteroid and immunosuppressant use decreased over time. CONCLUSIONS: Favourable safety profile and treatment responses with belimumab were maintained for ≤7 years in Japanese patients with SLE.

Negatively charged amino acids in the stalk region of membrane proteins reduce ectodomain shedding.

Ectodomain shedding is a post-translational modification mechanism by which the entire extracellular domain of membrane proteins is liberated through juxtamembrane processing. Because shedding rapidly and irreversibly alters the characteristics of cells, this process is properly regulated. However, the molecular mechanisms governing the propensity of membrane proteins to shedding are largely unknown. Here, we present evidence that negatively charged amino acids within the stalk region, an unstructured juxtamembrane region at which shedding occurs, contribute to shedding susceptibility. We show that two activated leukocyte cell adhesion molecule (ALCAM) protein variants produced by alternative splicing have different susceptibilities to ADAM metallopeptidase domain 17 (ADAM17)-mediated shedding. Of note, the inclusion of a stalk region encoded by a 39-bp-long alternative exon conferred shedding resistance. We found that this alternative exon encodes a large proportion of negatively charged amino acids, which we demonstrate are indispensable for conferring the shedding resistance. We also show that the introduction of negatively charged amino acids into the stalk region of shedding-susceptible ALCAM variant protein attenuates its shedding. Furthermore, we observed that negatively charged amino acids residing in the stalk region of Erb-B2 receptor tyrosine kinase 4 (ERBB4) are indispensable for its shedding resistance. Collectively, our results indicate that negatively charged amino acids within the stalk region interfere with the shedding of multiple membrane proteins. We conclude that the composition of the stalk region determines the shedding susceptibility of membrane proteins.

Predictors of Long-term Outcomes in Patients With Connective Tissue Disease Associated With Pulmonary Arterial Hypertension.

BACKGROUND/OBJECTIVE: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by increased pulmonary arterial pressure and pulmonary vascular resistance that can lead to right-sided heart failure. Connective tissue disease-associated PAH (CTD-PAH) often has poorer outcomes than idiopathic or hereditary PAH, suggesting the presence of non-PAH factors that could affect the prognoses. This cohort study aimed to identify prognostic factors for CTD-PAH management. METHODS: Medical records from April 1999 to November 2014 were reviewed to determine the time from treatment initiation to the occurrence of a clinically worsening event and the time elapsed until death. Data at baseline and the final assessment were used to identify prognostic factors associated with events using univariate and multivariate analyses by the stepwise Cox regression method. RESULTS: In 36 patients with CTD-PAH analyzed, the proportions with no clinically worsening events at 1, 2, and 3 years after treatment initiation were 62%, 52%, and 45%, respectively, with survival rates of 88%, 77%, and 77%, respectively. The regression model showed that reduced hemoglobin at baseline, reduced qR pattern in electrocardiogram lead V1, increased 60-minute erythrocyte sedimentation rate, and increased mean pulmonary arterial pressure at the final assessment were risk factors that were significantly associated with clinical worsening. For survival, no prognostic factor was identifiable. CONCLUSIONS: Hemodynamic and non-PAH factors, such as anemia, nutritional status, and inflammatory activity of the underlying CTD, which are not listed in the risk assessment table of PAH guidelines, should be strictly controlled to improve the prognosis of patients with CTD-PAH. A more multifactorial treatment strategy should be developed.

Redox-Induced Modulation of Exchange Interaction in a High-Spin Ground-State Diradical/Triradical System.

A triplet ground-state diradical molecule, bis(nitronyl nitroxide)-substituted diphenyldihydrophenazine (1.. ), that can be converted into a one-electron oxidized species, 1…+ , in the quartet ground state has been developed. Surprisingly, these species, 1.. and 1…+ , can be used under ambient conditions because they are reasonably stable under aerobic conditions, even in solution. The temperature-dependent magnetic susceptibilities reveal that 1.. and 1…+ are in the triplet state, with a weak exchange interaction (J1 /kB = +3.1 K) and quartet ground state with a strong exchange interaction (J2 /kB = +160 K), respectively. The interconversion between the neutral and one-electron oxidized species can be realized through electrochemical reactions. Significantly different absorption bands in the near-IR region newly appeared in the electronic spectra acquired during electrochemical oxidation/reduction.

Intergenerational gaps in Mexican American values trajectories: Associations with parent-adolescent conflict and adolescent psychopathology.

Growth mixture modeling with a sample of 749 Mexican heritage families identified parallel trajectories of adolescents' and their mothers' heritage cultural values and parallel trajectories of adolescents' and their fathers' heritage cultural values from Grades 5 to 10. Parallel trajectory profiles were then used to test cultural gap-distress theory that predicts increased parent-adolescent conflict and adolescent psychopathology over time when adolescents become less aligned with Mexican heritage values compared to their parents. Six similar parallel profiles were identified for the mother-youth and father-youth dyads, but only one of the six was consistent with the hypothesized problem gap pattern in which adolescents' values were declining over time to become more discrepant from their parents. When compared to families in the other trajectory groups as a whole, mothers in the mother-adolescent problem gap trajectory group reported higher levels of mother-adolescent conflict in the 10th grade that accounted for subsequent increases in internalizing and externalizing symptoms assessed in 12th grade. Although the findings provided some support for cultural gap-distress predictions, they were not replicated with adolescent report of conflict nor with the father-adolescent trajectory group analyses. Exploratory pairwise comparisons between all six mother-adolescent trajectory groups revealed additional differences that qualified and extended these findings.

Psychobehavioral Profiles to Assist Tailoring of Interventions for Patients With Hypertension: Latent Profile Analysis.

BACKGROUND: Practice guidelines advocate combining pharmacotherapy with lifestyle counseling for patients with hypertension. To allow for appropriate tailoring of interventions to meet individual patient needs, a comprehensive understanding of baseline patient characteristics is essential. However, few studies have empirically assessed behavioral profiles of hypertensive patients in Web-based lifestyle counseling programs. OBJECTIVE: The objectives of this study were to (1) specify baseline psychobehavioral profiles of patients with hypertension who were enrolled in a Web-based lifestyle counseling trial, and (2) examine mean differences among the identified profile groups in demographics, psychological distress, self-reported self-care behaviors, physiological outcomes, and program engagement to determine prognostic implications. METHODS: Participants (N=264; mean age 57.5 years; 154/264, 58.3% female; 193/264, 73.1% white) were recruited into a longitudinal, double-blind, randomized controlled trial, designed to evaluate an online lifestyle intervention for hypertensive patients. A series of latent profile analyses identified psychobehavioral profiles, indicated by baseline measures of mood, motivation, and health behaviors. Mean differences between profile groups were then explored. RESULTS: A 2-class solution provided the best model fit (the Bayesian information criterion (BIC) is 10,133.11; sample-size adjusted BIC is 10,006.54; Lo-Mendell-Rubin likelihood ratio test is 65.56, P=.001). The 2 profile groups were (1) adaptive adjustment, marked by low distress, high motivation, and somewhat satisfactory engagement in health behaviors and (2) affectively distressed, marked by clinically significant distress. At baseline, on average, affectively distressed patients had lower income, higher body mass index, and endorsed higher stress compared with their adaptive adjustment counterparts. At 12-months post intervention, treatment effects were sustained for systolic blood pressure and Framingham risk index in the adaptive adjustment group, and those in the adaptive adjustment group were 2.4 times more likely to complete the 12-month intervention study, compared with their affectively distressed counterparts. CONCLUSIONS: Interventions for patients who are adaptively adjusted may differ in focus from those designed for the affectively distressed patients. As such, this study underscores the importance of identifying psychobehavioral profiles, as they allow for evidence-based tailoring of lifestyle counseling programs for patients with hypertension. TRIAL REGISTRATION: ClinicalTrials.gov NCT01541540; https://clinicaltrials.gov/ct2/show/NCT01541540 (Archived by WebCite at http://www.webcitation.org/6yzZYZcWF).

Tenascin-C-derived peptide TNIIIA2 highly enhances cell survival and platelet-derived growth factor (PDGF)-dependent cell proliferation through potentiated and sustained activation of integrin α5ß1.

Tenascin-C is an adhesion modulatory matrix protein that is highly expressed in tumors; however, its biochemical activity involved in tumorigenesis is not fully understood. On the other hand, increasing evidence indicates the importance of integrin α5ß1 in cancer development. We previously demonstrated that tenascin-C harbors a functional site that can be released as a proadhesive peptide such as TNIIIA2. Peptide TNIIIA2 is capable of inducing activation of ß1-integrins including α5ß1 via syndecan-4. In this study the proadhesive effect of TNIIIA2 was characterized by potentiated and sustained activation of integrin α5ß1. Based on this effect, TNIIIA2 rendered nontransformed fibroblasts (NIH3T3) resistant to serum deprivation-elicited anoikis through activation of the Akt/Bcl-2 pathway. Moreover, TNIIIA2 hyperstimulated PDGF-dependent proliferation of NIH3T3 by activating integrin α5ß1. Tenascin-C, a parental protein of TNIIIA2, also stimulated PDGF-dependent proliferation, which was blocked by a matrix metalloproteinase-2/9 inhibitor and an anti-TNIIIA2 function-blocking antibody, suggesting proteolytic exposure of the proadhesive effect of TNIIIA2. Mechanistic analyses revealed that TNIIIA2 induced a lateral association of PDGF receptor ß with the molecular complex of activated integrin α5ß1 and syndecan-4 in the membrane microdomains enriched with cholesterol/caveolin-1, resulting in prolonged activation of PDGF receptor ß and the subsequent Ras/mitogen-activated protein kinase pathway in a PDGF-dependent manner. Of note, TNIIIA2 induced continuous proliferation in NIH3T3 in an integrin α5ß1-dependent manner even after they formed a confluent monolayer. Thus, it was proposed that tenascin-C might be involved in deregulated cell growth through potentiated and sustained activation of integrin α5ß1 after exposure of the proadhesive effect of TNIIIA2.

Dependence of photoinduced bending behavior of diarylethene crystals on irradiation wavelength of ultraviolet light.

The dependence of the photoinduced bending behavior of diarylethene crystals on the ultraviolet light irradiation wavelength was investigated. When irradiated with 365 nm light, a crystal of 1,2-bis(5-methyl-2-phenyl-4-thiazolyl)perfluorocyclopentene (1a) bends toward the incident light. On the other hand, when irradiated with 380 nm light, the crystal of 1a first bends away from the light source and then bends toward the incident light. To explain this bending behavior, we propose a comprehensive mechanism based on the depth of the photochromic reaction from the crystal surface. This mechanism is successfully supported by the change of cell parameters associated with the photochromic reaction upon irradiation with 380 nm light, which was determined by in situ X-ray crystallographic analysis.

Soy-Based High-Protein Spheric Foods with the Appearance of Familiar Sugary Snacks.

Excessive consumption of sugary foods increases the likelihood of obesity, as well as the preventable risk of lifestyle illnesses such as diabetes and cardiovascular diseases. Frequent intake of sweet snacks is considered to increase the risk of overweight/obesity in industrial nations. However, we cannot stop snacking against our better judgment. Therefore, in this study, we sought to develop high-protein, low-carb "mock snacks" to satisfy snack lovers' appetites and nutrition. Soy protein-based, ball-shaped food products with 57.7% (w/w) protein and 3.6% sugar have been developed. The addition of canola oil made them melty in the mouth without sacrificing their crispiness. Moreover, evaluation of the surface topography of the "soy balls" by 3D laser scanning demonstrated their high degree of sphericity. Conclusively, the snacks developed here may be one of the healthy alternatives for the current sugary ones.

Assembly of anionic silver nanoclusters with controlled packing structures through site-specific ionic bridges.

The assembly of metal nanoclusters (NCs) into crystalline lattice structures is of interest in the development of NC-based functional materials. Here we demonstrate that the assembled structures of tri-anionic tetrahedral symmetric [Ag29(BDT)12]3- (Ag29 NC, BDT: 1,3-benzenedithiol) NCs are controlled into a polyethylene-like zigzag chain and a "poly-ring-fused-cyclohexane"-like honeycomb arrangement through ionic interactions with alkali metal cations such as K+ and Cs+. The site-specific binding of alkali metal ions on the tetrahedrally arranged binding sites of Ag29 NCs successfully connects the adjacent NCs into various packing modes. The number and type of bridges between NCs determine the Ag29 NC packing structures, which are affected by the solvent species, enabling the transformation of packing modes in the single-crystalline state. The photoluminescence (PL) properties of the crystals responded to the packing modes of the NCs in terms of anisotropy and bridge linkage style inducing a varied degree of relaxation of the excited state depending on the relocation mobility of alkali metal ions in the crystals.

Cyclic-di-AMP confers an invasive phenotype on Escherichia coli through elongation of flagellin filaments.

BACKGROUND: Adherent-invasive Escherichia coli (AIEC) is isolated from patients with Crohn's disease (CD). AIEC can invade the intestinal epithelium, suggesting that it is involved in the development and pathogenesis of CD. However, the mechanism by which AIEC acquired the invasive phenotype remains unknown. RESULTS: This study was designed to examine the mechanisms of AIEC invasiveness. We found that the flagellin (fliC) expression in AIEC was two-fold higher than that in non-AIEC strains, and this overexpression induced the formation of long-filament flagellin. Deletion of fliC in the AIEC LF82 strain resulted in the disappearance of flagellar filaments and attenuated the motility and invasive ability of the bacterium, suggesting that the formation of long filament flagellin induced by increased fliC expression is required by AIEC to invade the intestinal epithelium. In AIEC and non-AIEC K12 strains cultured in the presence of cyclic-di-AMP (c-di-AMP), the expression of fliC was enhanced, and flagellar filaments were elongated. Stimulation with c-di-AMP enhanced the bacterial motility and ability to invade epithelial cells, even in the non-AIEC K12 strain. CONCLUSIONS: Our findings show that c-di-AMP confers an AIEC-like phenotype on non-AIEC strains by enhancing the expression of fliC. The results should be useful for understanding the pathogenesis of CD.

Macrophage-depleted young mice are beneficial in vivo models to assess the translocation of Klebsiella pneumonia from the gastrointestinal tract to the liver in the elderly.

Pathobionts are commensal intestinal microbiota capable of causing systemic infections under specific conditions, such as environmental changes or aging. However, it is unclear how pathobionts are recognized by the intestinal mucosal immune system under physiological conditions. This study demonstrates that the gut pathobiont Klebsiella pneumoniae causes injury to the epithelium and translocates to the liver in specific pathogen-free mice treated with clodronate-liposomes that depleted macrophages. In the clodronate-liposome-treated mice, indigenous classical K. pneumoniae (cKp) with non-K1/K2 capsular serotypes were isolated from the liver, indicating that gut commensal cKp translocated from the gastrointestinal tract to the liver due to the depletion of intestinal macrophages. Oral inoculation of isolated cKp to clodronate-liposome-treated mice significantly reduced the survival rates compared to that of non-treated mice. Our findings demonstrate that intestinal mucosal macrophages play a pivotal role in sensing commensal cKp and suppressing their translocation to the liver. This study demonstrates that clodronate-liposome-treated mouse models are effective for screening and evaluating drugs that prevent the translocation of cKp to the liver, providing new insights into the development of preventive protocols against K. pneumoniae infection.

Selective deprotection method of N-phenylcarbamoyl group.

We report an improved method for the selective deprotection of the N-phenylcarbamoyl group, which yields the corresponding alcohol without affecting other protecting groups. Deprotection was performed using di-tert-butyl dicarbonate and tetra-n-butylammonium nitrite (Boc2O and Bu4NNO2) in pyridine at room temperature. This method is also effective for deprotecting the fluorous N-phenylcarbamoyl group.

Prenatal expectations in Mexican American women: development of a culturally sensitive measure.

Prenatal expectations describe various domains a woman envisions in preparation for her role as a new mother and influence how women transition into the maternal role. Although the maternal role is strongly influenced by the prevailing familial and sociocultural context, research characterizing prenatal expectations in ethnic minority and low-income women is lacking. As part of the largest growing minority group in the USA, Latina mothers represent an important group to study. Two hundred and ten low-income Mexican American women were administered the Prenatal Experiences Scale for Mexican Americans (PESMA) that was adapted to capture specific cultural aspects of prenatal expectations. Measures of current support, prenatal depressive symptoms, and other sociodemographic characteristics were also completed to assess validity. Exploratory factor analysis identified three underlying factors of prenatal expectations: paternal support, family support, and maternal role fulfillment. Associations among these subscales and demographic and cultural variables were conducted to characterize women who reported higher and lower levels of expectations. The PESMA demonstrated good concurrent validity when compared to measures of social support, prenatal depressive symptoms, and other sociodemographic constructs. A culturally sensitive measure of prenatal expectations is an important step towards a better understanding of how Mexican American women transition to the maternal role and identify culturally specific targets for interventions to promote maternal health.

Effect of melamine foam cleaning on the surface condition of composite resin artificial teeth.

PURPOSE: The purpose of this study was to examine the abrasive and cleaning effects of melamine foam and other cleaning agents on the surfaces of composite resin artificial tooth specimens. MATERIALS AND METHODS: A stained composite resin artificial tooth in a used denture was cleaned using a denture brush and melamine foam, and the stain removal effect was evaluated macroscopically. Next, 5 types of cleaning material (fourfold-compression melamine foam, MEL; brush with water, BRU; denture dentifrice without abrasive, POL; denture dentifrice with abrasive, TAF; conventional dentifrice, AQU) and 15 plate-shaped specimens made of composite resin for artificial teeth were used for wear tests. The surface roughness was measured using a laser scanning microscope. Furthermore, the surface properties were observed using a digital microscope. Surface roughness data were analyzed by two-way ANOVA followed by Tukey's test. RESULTS: Artificial tooth stains that could not be removed by brushing became removable using melamine foam. With regard to surface roughness in the context of the wear test, significant differences were not indicated between MEL and POL, whereas BRU-, TAF-, and AQU-treated specimens showed significantly increased surface roughness (p < 0.05). In the comparison among the cleaning materials, TAF- and AQU-treated specimens showed significantly rougher surfaces than those treated with MEL, BRU, and POL (p < 0.05). CONCLUSIONS: Macroscopic observations suggest that melamine foam would be effective for the removal of stains on composite resin artificial teeth. Traces of wear were not observed in specimens treated with melamine foam and the denture dentifrice not containing abrasives. It was suggested that these two materials would be desirable and useful to use for composite resin tooth cleaning.

Adherent-invasive E. coli - induced specific IgA limits pathobiont localization to the epithelial niche in the gut.

Background and aim: Adherent-invasive E. coli (AIEC) has been identified as a pathobiont associated with Crohn's disease (CD), that prefers to grow in inflammatory conditions. Although the colonization by AIEC is implicated in the progression of the disease and exacerbates inflammation in murine colitis models, the recognition and response of host immunity to AIEC remains elusive. Methods: Antibiotic treated female C57BL/6 mice were inoculated by commensal E. coli and LF82 AIEC strains. Luminal-IgA fractions were prepared from feces and their binding to AIEC and other strains was assessed to confirm specificity. IgA binding to isogenic mutant strains was performed to identify the functional molecules that are recognized by AIEC specific IgA. The effect of IgA on epithelial invasion of LF82 strain was confirmed using in vitro invasion assay and in vivo colonization of the colonic epithelium. Results: Persistent colonization by AIEC LF82 induced secretion of luminal IgA, while commensal E. coli strain did not. Induced anti-LF82 IgA showed specific binding to other AIEC strains but not to the commensal, non-AIEC E. coli strains. Induced IgA showed decreased binding to LF82 strains with mutated adhesin and outer membrane proteins which are involved in AIEC - epithelial cell interaction. Consistently, LF82-specific IgA limited the adhesion and invasion of LF82 in cultured epithelial cells, which seems to be required for the elimination in the colonic epithelium in mice. Conclusion: These results demonstrate that host immunity selectively recognizes pathobiont E. coli, such as AIEC, and develop specific IgA. The induced IgA specific to pathobiont E. coli, in turn, contributes to preventing the pathobionts from accessing the epithelium.