In some patients with type 1 diabetes the dose of insulin required to achieve euglycemia is substantially reduced soon after diagnosis. This partial remission is associated with β-cell function and good glucose control. The purpose of this study was to assess whether frequencies of CD4+ T cell subsets in children newly diagnosed with type 1 diabetes are associated with length of partial remission. We found that the frequency of CD4+ memory cells, activated Treg cells and CD25+ cells that express a high density of the IL-7 receptor, CD127 (CD127hi) are strongly associated with length of partial remission. Prediction of length of remission via Cox regression is significantly enhanced when CD25+ CD127hi cell frequency is combined with either Insulin Dependent Adjusted A1c (IDAA1c), or glycosylated hemoglobin (HbA1c), or C-peptide levels at diagnosis. CD25+ CD127hi cells do not express Foxp3, LAG-3 and CD49b, indicating that they are neither Treg nor Tr1 cells.

Mucins are present in mucosal membranes throughout the body and play a key role in the microbe clearance and infection prevention. Understanding the metabolic responses of pathogens to mucins will further enable the development of protective approaches against infections. We update the genome-scale metabolic network reconstruction (GENRE) of one such pathogen, Pseudomonas aeruginosa PA14, through metabolic coverage expansion, format update, extensive annotation addition, and literature-based curation to produce iPau21. We then validate iPau21 through MEMOTE, growth rate, carbon source utilization, and gene essentiality testing to demonstrate its improved quality and predictive capabilities. We then integrate the GENRE with transcriptomic data in order to generate context-specific models of P. aeruginosa metabolism. The contextualized models recapitulated known phenotypes of unaltered growth and a differential utilization of fumarate metabolism, while also revealing an increased utilization of propionate metabolism upon MUC5B exposure. This work serves to validate iPau21 and demonstrate its utility for providing biological insights.

Microbial communities affect many facets of human health and well-being. Naturally occurring bacteria, whether in nature or the human body, rarely exist in isolation.