Publication highlights

Scientists at the Crick have untangled a complex pathway that could help explain how interactions between microorganisms and the body’s immune defences lead to gut inflammation and colitis. They deleted transcription factors c-Maf, Blimp-1 or both in T cells in mice, observing that, when combined with infection with Helicobacter hepaticus bacteria, IL-10 activity in T cells was reduced and inflammation progressed. When both proteins were removed, the mice developed severe colitis. By studying data from colon biopsies of patients with IBD, the scientists showed that there were similarities in the genes expressed in humans with IBD and the mice with bacteria-induced inflammation resulting from an absence of either c-Maf or Blimp-1.

Using advanced bioinformatics approaches, we deciphered the global transcriptional response in the lungs of mice infected or challenged with a broad spectrum of infectious pathogens, including parasites, bacteria, viruses, fungi, or allergens; we also determined to what extent each of these responses is preserved in the blood. We demonstrated a unique global transcriptional signature for each of the different diseases in both lung and blood. The lung transcriptional signatures showed a gradation, ranging from IFN-inducible gene clusters, to those associated with granulocyte/neutrophil/IL-17 dominated genes, to responses dominated by expression of genes encoding TH2 cytokines, mast cells and B cells.

An important factor in determining the outcome of M. tuberculosis infection was identified in new research from the O’Garra lab. The team found that the cytokine type I interferon-induced neutrophil extracellular trap (NET) formation promotes bacterial growth and disease severity.