GL7 ligand expression defines a novel subset of CD4 T cells in lungs recovered from pneumococcus.

Streptococcus pneumoniae is the most common etiology of bacterial pneumonia, one of the leading causes of death in children and the elderly worldwide. During non-lethal infections with S. pneumoniae, lymphocytes accumulate in the lungs and protect against reinfection with serotype-mismatched strains.

Neutrophil Extracellular Traps as an Exacerbating Factor in Bacterial Pneumonia.

Neutrophils are capable of extruding neutrophil extracellular traps (NETs), a network of granule proteins and chromatin material, upon activation. NETs provide defense against extracellular microbes, but histones in NETs can also induce cytotoxicity and activate inflammatory responses. The relevance of NETs to bacterial pneumonias is beginning to be defined.

CPHEN-011: Comprehensive phenotyping of murine lung resident lymphocytes after recovery from pneumococcal pneumonia.

Recovery from pneumococcal (Spn) pneumonia induces development of tissue resident memory CD4 T cells, B cells, and antibody secreting plasma cells in experienced lungs. These tissue resident lymphocytes confer protection against subsequent lethal challenge by serotype mismatched Spn (termed as heterotypic immunity). While traditional flow cytometry and gating strategies support premeditated identification of cells using a limited set of markers, discovery of novel tissue resident lymphocytes necessitates stable platforms that can handle larger sets of phenotypic markers and lends itself to unbiased clustering approaches.

Antigen presentation by lung epithelial cells directs CD4 T cell function and regulates barrier immunity.

Barrier tissues are populated by functionally plastic CD4 resident memory T (T) cells. Whether the barrier epithelium regulates CD4 T cell locations, plasticity and activities remains unclear. Here we report that lung epithelial cells, including distinct surfactant protein C (SPC)MHC epithelial cells, function as anatomically-segregated and temporally-dynamic antigen presenting cells.

Unique Roles for Phosphodiesterase 2 in Cyclic di-AMP Catabolism and Macrophage Responses.

Cyclic di-AMP (c-di-AMP) is an important signaling molecule for pneumococci, and as a uniquely prokaryotic product it can be recognized by mammalian cells as a danger signal that triggers innate immunity. Roles of c-di-AMP in directing host responses during pneumococcal infection are only beginning to be defined. We hypothesized that pneumococci with defective c-di-AMP catabolism due to phosphodiesterase deletions could illuminate roles of c-di-AMP in mediating host responses to pneumococcal infection.

Lung CD4 resident memory T cells remodel epithelial responses to accelerate neutrophil recruitment during pneumonia.

Previous pneumococcal experience establishes lung-resident IL-17A-producing CD4 memory T cells that accelerate neutrophil recruitment against heterotypic pneumococci. Herein, we unravel a novel crosstalk between CD4 T cells and lung epithelial cells underlying this protective immunity. Depletion of CD4 cells in pneumococcus-experienced mice diminished CXCL5 (but not CXCL1 or CXCL2) and downstream neutrophil accumulation in the lungs.