This study describes the features of LRTIs associated with newly identified viruses in children, compared with those associated with known viruses. Additional investigations are required to define the role of HBoV in LRTI.

Dendritic cells (DCs) that orchestrate mucosal immunity have been studied in mice. Here we characterize human gut DC populations, and define their relationship to previously studied human and mouse DCs. CD103+Sirpα− DCs were related to human blood CD141+ and to mouse intestinal CD103+CD11b− DCs and expressed markers of cross-presenting DCs. CD103+Sirpα+ DCs aligned with human blood CD1c+ DCs and mouse intestinal CD103+CD11b+ DCs and supported regulatory T cell induction. Both CD103+ DC subsets induced TH17 cells, while CD103−Sirpα+ DCs induced TH1 cells. Comparative transcriptomics revealed conserved transcriptional programs among CD103+ DC subsets and uncovered a selective role for Bcl-6 and Blimp-1 in CD103+Sirpα− and intestinal CD103+CD11b+ DC specification, respectively. These results highlight evolutionarily conserved and divergent programming of intestinal DCs.

Spinal cord injury (SCI) causes a permanent neurological disability, and no satisfactory treatment is currently available. After SCI, pro-nerve growth factor (proNGF) is known to play a pivotal role in apoptosis of oligodendrocytes, but the cell types producing proNGF and the signaling pathways involved in proNGF production are primarily unknown. Here, we show that minocycline improves functional recovery after SCI in part by reducing apoptosis of oligodendrocytes via inhibition of proNGF production in microglia. After SCI, the stress-responsive p38 mitogen-activated protein kinase (p38MAPK) was activated only in microglia, and proNGF was produced by microglia via the p38MAPK-mediated pathway. Minocycline treatment significantly reduced proNGF production in microglia in vitro and in vivo by inhibition of the phosphorylation of p38MAPK. Furthermore, minocycline treatment inhibited p75 neurotrophin receptor expression and RhoA activation after injury. Finally, minocycline treatment inhibited oligodendrocyte death and improved functional recovery after SCI. These results suggest that minocycline may represent a potential therapeutic agent for acute SCI in humans.

Phagocytosis of apoptotic cells usually results in an anti-inflammatory state with inhibition of proinflammatory cytokines such as IL-12. How apoptotic cell-derived signals regulate IL-12 gene expression is not understood. We demonstrate that cell-cell contact with apoptotic cells is sufficient to induce profound inhibition of IL-12 production by activated macrophages. Phosphatidylserine could mimic the inhibitory effect. The inhibition does not involve autocrine or paracrine actions of IL-10 and TGF-beta. We report the identification, purification, and cloning of a novel zinc finger nuclear factor, named GC binding protein (GC-BP), that is induced following phagocytosis of apoptotic cells by macrophages or by treatment with phosphatidylserine. GC-BP selectively inhibits IL-12 p35 gene transcription by binding to its promoter in vitro and in vivo, thus decreasing IL-12 production. Blocking GC-BP by RNA interference restores IL-12 p35 transcription and IL-12 p70 synthesis. Finally, GC-BP itself undergoes functionally significant tyrosine dephosphorylation in response to apoptotic cells.

A single, multidrug-resistant strain was responsible for increased incidence of this serotype before introduction of the pneumococcal 7-valent conjugate vaccine.