RESUMEN
Chronic hepatitis B virus (HBV) infection remains a serious disease, mainly due to its severe pathological consequences, which are difficult to cure using current therapies. When the immune system responds to hepatocytes experiencing rapid HBV replication, effector cells (such as HBV-specific CD8+ T cells, NK cells, NKT cells, and other subtypes of immune cells) infiltrate the liver and cause hepatitis. However, the precise recruitment of these cells remains unclear. In the present study, we found that the cytoplasm-translocated Ku70/80 complex in liver-derived cells sensed cytosolic HBV DNA and promoted hepatitis-associated chemokine secretion. Upon sensing HBV DNA, DNA-dependent protein kinase catalytic subunit and PARP1 were assembled. Then, IRF1 was activated and translocated into the nucleus, which upregulated CCL3 and CCL5 expression. Because CCR5, a major chemokine receptor for CCL3 and CCL5, is known to be critical in hepatitis B, Ku70/80 sensing of HBV DNA likely plays a critical role in immune cell recruitment in response to HBV infection.
RESUMEN
The period of immune deficiency following bone marrow transplantation (BMT) results in a susceptibility to opportunistic infections and remains a growing obstacle in improving the efficacy of BMT. Neuroendocrine hormones have been shown to affect numerous immunologic and hematologic responses after in vivo administration. We investigated whether neuroendocrine hormones, notably prolactin (PRL), could be administered after BMT and result in improved immunologic recovery. Mice were given lethal total body irradiation followed with a congeneic or a syngeneic BMT. Some groups then received recombinant human PRL (rhPRL) daily for 3 weeks. Effects on immune reconstitution and function were then monitored. The results show that PRL could increase thymic cellularity and donor T-cell reconstitution after congeneic BMT. Increases in B cells and myeloid progenitors were also observed. Mitogenic responses by both T and B cells were observed after PRL treatment. These results suggest that PRL may be of use to promote immune and myeloid reconstitution after BMT.