No abstract

Mycoplasma pneumoniae is an important etiology of CAP in children 5 years or younger. They had a longer length of hospitalization, higher inflammatory responses, and more complications, compared to children older than 5 years.

Since its first identification in Scotland, over 1000 cases of unexplained pediatric hepatitis in children have been reported worldwide, including 278 cases in the UK 1 . Here we report investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator subjects, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in liver, blood, plasma or stool from 27/28 cases. We found low levels of Adenovirus (HAdV) and Human Herpesvirus 6B (HHV-6B), in 23/31 and 16/23 respectively of the cases tested. In contrast, AAV2 was infrequently detected at low titre in blood or liver from control children with HAdV, even when profoundly immunosuppressed.AAV2, HAdV and HHV-6 phylogeny excluded emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T-cells and B-lineage cells.Proteomic comparison of liver tissue from cases and healthy controls, identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins.HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and in severe cases HHV-6B, may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children.

A proinflammatory role for glycogen synthase kinase 3␤ (GSK-3␤) has been demonstrated. Here, we addressed its roles on heat-inactivated Staphylococcus aureus-induced microglial inflammation. Heat-inactivated S. aureus induced tumor necrosis factor alpha (TNF-␣) and nitric oxide (NO) production, at least in part, via a Toll-like receptor 2-regulated pathway. Neutralization of TNF-␣ largely blocked heat-inactivated S. aureus-induced NO. Heat-inactivated S. aureus activated GSK-3␤, and inhibiting GSK-3␤ reduced TNF-␣ production as well as inducible NO synthase (iNOS)/NO biosynthesis. While activation of NF-B was essential for heat-inactivated S. aureus-induced TNF-␣ and NO, inhibiting GSK-3␤ blocked heat-inactivated S. aureusinduced NF-B p65 nuclear translocation. Additionally, inhibiting GSK-3␤ enhanced heat-inactivated S. aureus-induced interleukin-10 (IL-10) production (IL-10 is an anti-inflammatory cytokine which inhibits TNF-␣ production). Neutralization of IL-10 reduced TNF-␣ downregulation caused by GSK-3␤ inhibition. These results suggest that GSK-3␤ regulates heat-inactivated S. aureus-induced TNF-␣ and NO production in microglia mainly by activating NF-B and probably by inhibiting IL-10.