Microbiota-derived inosine programs protective CD8 T cell responses against influenza in newborns.

The immunological defects causing susceptibility to severe viral respiratory infections due to early-life dysbiosis remain ill-defined. Here, we show that influenza virus susceptibility in dysbiotic infant mice is caused by CD8 T cell hyporesponsiveness and diminished persistence as tissue-resident memory cells. We describe a previously unknown role for nuclear factor interleukin 3 (NFIL3) in repression of memory differentiation of CD8 T cells in dysbiotic mice involving epigenetic regulation of T cell factor 1 (TCF 1) expression.

The balance between protective and pathogenic immune responses to pneumonia in the neonatal lung is enforced by gut microbiota.

Although modern clinical practices such as cesarean sections and perinatal antibiotics have improved infant survival, treatment with broad-spectrum antibiotics alters intestinal microbiota and causes dysbiosis. Infants exposed to perinatal antibiotics have an increased likelihood of life-threatening infections, including pneumonia. Here, we investigated how the gut microbiota sculpt pulmonary immune responses, promoting recovery and resolution of infection in newborn rhesus macaques.

Replication and meta-analyses nominate numerous eosinophilic esophagitis risk genes.

Background: Eosinophilic esophagitis (EoE) is an emerging, chronic, rare allergic disease associated with marked eosinophil accumulation in the esophagus. Previous genome-wide association studies have provided strong evidence for 3 genome-wide susceptibility loci.

Objective: We sought to replicate known and suggestive EoE genetic risk loci and conduct a meta-analysis of previously reported data sets.

Early life antibiotic exposure and host health: Role of the microbiota-immune interaction.

The neonatal population is at high risk for infections secondary to a unique, developing immune system. While a multitude of factors direct the development of the immune system, the role of environmental exposures on the microbiota may play a critical and potentially modifiable role. Recent evidence suggests that the disruption of the microbiota through the use of antibiotics not only leads to an immediately increased risk for neonatal complications but also long-term health issues related to autoimmune and inflammatory diseases.

Insulin-like Growth Factor 1 Supports a Pulmonary Niche that Promotes Type 3 Innate Lymphoid Cell Development in Newborn Lungs.

Type 3 innate lymphoid cells (ILC3s) are critical for lung defense against bacterial pneumonia in the neonatal period, but the signals that guide pulmonary ILC3 development remain unclear. Here, we demonstrated that pulmonary ILC3s descended from ILC precursors that populated a niche defined by fibroblasts in the developing lung. Alveolar fibroblasts produced insulin-like growth factor 1 (IGF1), which instructed expansion and maturation of pulmonary ILC precursors.