Biology subjects

Guillen, J. V.

Publications and source records attributed to Guillen, J. V..

2 recordsLinked to original sources

bioRxiv2022

Cellular sources and targets of type I interferons that drive susceptibility to tuberculosis

Mycobacterium tuberculosis (Mtb) causes 1.6 million deaths annually. Active tuberculosis correlates with a neutrophil-driven type I interferon (IFN) signature, but the cellular mechanisms underlying tuberculosis pathogenesis remain poorly understood. We found interstitial macrophages (IMs) and plasmacytoid dendritic cells (pDCs) are dominant producers of type I IFN during Mtb infection in mice and non-human primates, and pDCs localize near human Mtb granulomas. Depletion of pDCs reduces Mtb burdens, implicating pDCs in tuberculosis pathogenesis. During IFN-driven disease, we observe abundant DNA-containing neutrophil extracellular traps (NETs) known to activate pDCs. Cell type-specific disruption of the type I IFN receptor suggests IFNs act on IMs to inhibit Mtb control. Single cell RNA-seq indicates type I IFN-responsive cells are defective in their response to IFN{gamma}, a cytokine critical for Mtb control. We propose pDC-derived type I IFNs act on IMs to drive bacterial replication, further neutrophil recruitment, and active tuberculosis disease.

immunology↗

bioRxiv2022

Paracrine signaling by pancreatic delta cells determines the glycemic set point in mice

Pancreatic islets contain several endocrine cell types that coordinate to maintain blood glucose homeostasis. While {beta} and cells are thought to be the main drivers of glucose homeostasis through insulin and glucagon secretion respectively, the contribution of {delta} cells and somatostatin (SST) secretion to establishing the glycemic set point remains unresolved. Here we remove local SST signaling from {delta} cells within the pancreatic islet to investigate their contribution to the glycemic set point. Our data demonstrate that ablating {delta} cells or SST leads to a sustained decrease in the glycemic set point. This coincides with a decreased glucose threshold for insulin response from {beta} cells, leading to increased insulin secretion to the same glucose challenge. In contrast, cell ablation had no effect on glycemic set point. Collectively, these data establish the physiological role of {delta} cells in determining the glycemic set point through their interaction with {beta} cells.

physiology↗