Aspergillus terreus Spondylodiscitis in an Immunocompromised Child.

We report the case of a 12-year-old immunocompromised boy with spondylodiscitis of the thoracolumbar spine caused by Aspergillus terreus. Microbiologic diagnosis was confirmed by inoculation of aspiration fluid into blood culture bottles. Because of noncompliance, the patient was treated with extended voriconazole therapy (23 months) with regular serum drug concentration monitoring and intermittent direct observation therapy in an outpatient clinic. The Aspergillus genus contains species that are important causes of morbidity and mortality in immunocompromised hosts. Although the lung is the main target of invasive Aspergillosis, more severe forms such as Aspergillus osteomyelitis can occur. A. fumigatus is the most common cause of Aspergillus osteomyelitis, causing 55%-61% of all cases, whereas A. terreus causes 2.3%-2.8% of cases. The vertebral bodies are the most commonly affected sites, occurring in 46%-49% of cases., Here, we report the case of an immunocompromised 12-year-old boy with thoracolumbar spondylodiscitis caused by A. terreus.

Increased p190RhoGEF expression in activated B cells correlates with the induction of the plasma cell differentiation

Previously, we demonstrated that the p190 Rho guanine nucleotide exchange factor (p190RhoGEF) was induced following CD40 stimulation of B cells. In this study, we examined whether p190RhoGEF and a downstream effector molecule RhoA are required for B cell differentiation. Expression of p190RhoGEF positively correlated with the expression of surface markers and transcriptional regulators that are characteristic of mature B cells with plasma cell (PC) phenotypes. Moreover, either the overexpression of p190RhoGEF or the expression of a constitutively active RhoA drove cellular differentiation toward PC phenotypes. B cell maturation was abrogated in cells that overexpressed p190RhoGEF and a dominant-negative form of RhoA simultaneously. CD40-mediated maturation events were also abrogated in cells that overexpressed either dominant-negative p190RhoGEF or RhoA. Together, these data provide evidence that p190RhoGEF signaling through RhoA in CD40-activated B cells drives the induction of the PC differentiation.

Ligation of CD40 receptor in human B lymphocytes triggers the 5-lipoxygenase pathway to produce reactive oxygen species and activate p38 MAPK

Previously, we reported that CD40-induced production of reactive oxygen species (ROS) by NADPH oxidase requires the TNF receptor-associated factor (TRAF) 3, as well as the activities of phosphatidylinositol 3-kinase (PI3K) and Rac1. Here we investigated the possible mechanisms of the production of ROS after CD40 ligation in B cells. We describe an alternative ROS production pathway that is triggered by CD40 ligation, involves 5-lipoxygenase (5-LO), and results in activation of p38 MAPK. Our studies in Raji human B lymphomas revealed that CD40-induced ROS production by 5-LO also requires the activities of PI3K and Rac1. In contrast to the NADPH oxidase pathway, however, TRAF molecules are not required for the CD40-induced ROS production by 5-LO. The association of CD40 with 5-LO is dependent on CD40 ligation in Raji B cells, and co-immunoprecipitation experiments using epitope-tagged proteins transiently expressed in human embryonic kidney 293T cells revealed the role of the regulatory subunit of PI3K, p85, in this association. Collectively, these data suggest a separate pathway for the CD40-induced ROS production in B cells and demonstrate that this pathway requires 5-LO via direct association of p85 with both CD40 and 5-LO.