Background and Aims
The intestinal microbiota is closely associated with resident memory lymphocytes in mucosal tissue. We sought to understand how acquired cellular and humoral immunity to the microbiota differ in health versus inflammatory bowel disease [IBD].
Methods
Resident memory T cells [Trm] in colonic biopsies and local antibody responses to intraepithelial microbes were analysed. Systemic antigen-specific immune T and B cell memory to a panel of commensal microbes was assessed.
Results
Systemically, healthy blood showed CD4 and occasional CD8 memory T cell responses to selected intestinal bacteria, but few memory B cell responses. In IBD, CD8 memory T cell responses decreased although B cell responses and circulating plasmablasts increased. Possibly secondary to loss of systemic CD8 T cell responses in IBD, dramatically reduced numbers of mucosal CD8+ Trm and γδ T cells were observed. IgA responses to intraepithelial bacteria were increased. Colonic Trm expressed CD39 and CD73 ectonucleotidases, characteristic of regulatory T cells. Cytokines/factors required for Trm differentiation were identified, and in vitro-generated Trm expressed regulatory T cell function via CD39. Cognate interaction between T cells and dendritic cells induced T-bet expression in dendritic cells, a key mechanism in regulating cell-mediated mucosal responses.
Conclusions
A previously unrecognised imbalance exists between cellular and humoral immunity to the microbiota in IBD, with loss of mucosal T cell-mediated barrier immunity and uncontrolled antibody responses. Regulatory function of Trm may explain their association with intestinal health. Promoting Trm and their interaction with dendritic cells, rather than immunosuppression, may reinforce tissue immunity, improve barrier function, and prevent B cell dysfunction in microbiota-associated disease and IBD aetiology.
In neonates undergoing systemic-to-pulmonary artery shunt placement, approximately 10% underwent shunt intervention before discharge. Some factors, such as low birthweight, shunt size, noncardiac congenital abnormalities, and heterotaxy syndrome, may help identify patients at risk. Patients undergoing intervention experienced increased morbidity and mortality.
Background: Bacteroides thetaiotaomicron (Bt) is a prominent member of the human intestinal microbiota that, like all gram-negative bacteria, naturally generates nanosized outer membrane vesicles (OMVs) which bud off from the cell surface. Importantly, OMVs can cross the intestinal epithelial barrier to mediate microbe-host cell crosstalk involving both epithelial and immune cells to help maintain intestinal homeostasis. Here, we have examined the interaction between Bt OMVs and blood or colonic mucosa-derived dendritic cells (DC) from healthy individuals and patients with Crohn's disease (CD) or ulcerative colitis (UC). Results: In healthy individuals, Bt OMVs stimulated significant (p < 0.05) IL-10 expression by colonic DC, whereas in peripheral blood-derived DC they also stimulated significant (p < 0.001 and p < 0.01, respectively) expression of IL-6 and the activation marker CD80. Conversely, in UC Bt OMVs were unable to elicit IL-10 expression by colonic DC. There were also reduced numbers of CD103 + DC in the colon of both UC and CD patients compared to controls, supporting a loss of regulatory DC in both diseases. Furthermore, in CD and UC, Bt OMVs elicited a significantly lower proportion of DC which expressed IL-10 (p < 0.01 and p < 0.001, respectively) in blood compared to controls. These alterations in DC responses to Bt OMVs were seen in patients with inactive disease, and thus are indicative of intrinsic defects in immune responses to this commensal in inflammatory bowel disease (IBD). Conclusions: Overall, our findings suggest a key role for OMVs generated by the commensal gut bacterium Bt in directing a balanced immune response to constituents of the microbiota locally and systemically during health which is altered in IBD patients.
Pericardial effusion (PE) may require readmission after cardiac surgery and has been associated with postoperative morbidity and mortality. We sought to identify the prevalence and risk factors for postoperative PE requiring readmission in children. A retrospective analysis of the Pediatric Health Information System database was performed between January 1, 2003, and September 30, 2014. All patients ≤18 years old who underwent cardiac surgery were identified by ICD-9 codes. Those readmitted within 1 year with an ICD-9 code for PE were identified. Logistic regression analysis was performed to determine risk factors for PE readmissions. Of the 142,633 surgical admissions, 1535 (1.1%) were readmitted with PE. In multivariable analysis, older age at the initial surgical admission [odds ratio (OR) 1.17, p < 0.001], trisomy 21 (OR 1.24, p = 0.015), geographic region (OR 1.33-1.48, p ≤ 0.001), and specific surgical procedures [heart transplant (OR 1.82, p < 0.001), systemic-pulmonary artery shunt (OR 2.23, p < 0.001), and atrial septal defect surgical repair (OR 1.34, p < 0.001)] were independent risk factors for readmission with PE. Of readmitted patients, 44.2% underwent an interventional PE procedure. Factors associated with interventions included shorter length of stay (LOS) for the initial surgical admission (OR 0.85, p = 0.008), longer LOS for the readmission (OR 1.37, p < 0.001), and atrial septal defect surgery (OR 1.40, p = 0.005). In this administrative database of children undergoing cardiac surgery, readmissions for PE occurred after 1.1% of cardiac surgery admissions. The risk factors identified for readmissions and interventions may allow for improved risk stratification, family counseling, and earlier recognition of PE for children undergoing cardiac surgery.
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