Depletion of macrophages in mice results in higher dengue virus titers and highlights the role of macrophages for virus control

Monocytes and macrophages are target cells for dengue infection. Besides their potential role for virus replication, activated monocytes/macrophages produce cytokines that may be critical for dengue pathology. To study the in vivo role of monocytes and macrophages for virus replication, we depleted monocytes and macrophages in IFN‐αβγR knockout mice with clodronate liposomes before dengue infection. Although less virus was first recovered in the draining LN in the absence of macrophages, monocyte/macrophage depletion eventually resulted in a ten‐fold higher systemic viral titer. A massive infiltration of CD11b⁺CD11c^lowLy6C^low monocytes into infected organs was observed in parallel with increasing virus titers before viremia was controlled. Depletion of monocytes in the blood before or after local infection had no impact on virus titers, suggesting that monocytes are not required as “virus‐shuttles”. Our data provide evidence that systemic viremia is established independently of tissue macrophages present at the site of infection and blood monocytes. Instead, we demonstrate the importance of monocytes/macrophages for the control of dengue virus.     

Genesis of hepatic fibrosis and its biochemical markers

Liver fibrosis is characterized by an abnormal hepatic accumulation of extracellular matrix (ECM) that results from both increased deposition and reduced degradation of collagen fibres. Fibrotic liver injury results in activation of the hepatic stellate cell (HSC). Surrogate markers are gradually being substituted for biomarkers that reflect the complex balance between synthesis and degradation of the extracellular matrix. Once the hepatic stellate cell is activated, the preceding matrix changes and recurrent injurious stimuli will perpetuate the activated state. The ECM directs cellular differentiation, migration, proliferation and fibrogenic activation or deactivation. The metabolism of the extracellular matrix is closely regulated by matrix metalloproteinases (MMP) and their specific tissue inhibitors (TIMP). Although liver biopsy combined with connective tissue stains has been a mainstay of diagnosis, there is a need for less invasive methods. These diagnostic markers should be considered in combination with liver function tests, ultrasonography and clinical manifestations.     

Cortical grey matter volume and sensorimotor gating in schizophrenia

Prepulse inhibition (PPI) of the startle response, a cross-species measure of sensorimotor gating, provides a valuable tool to study the known inability of a large proportion of individuals with schizophrenia to effectively screen out irrelevant sensory input. The cortico-striato-pallido-thalamic circuitry is thought to be responsible for modulation of PPI in experimental animals. The involvement of this circuitry in human PPI is supported by observations of deficient PPI in a number of neuropsychiatric disorders that are characterised by abnormalities at some level in this circuitry, and findings of recent functional neuroimaging studies in healthy participants. The current study sought to investigate the structural neural correlates of PPI in a sample of 42 stable male outpatients with schizophrenia. Participants underwent magnetic resonance imaging (MRI) at 1.5T and were assessed (off-line) on acoustic PPI using electromyographic recordings of the orbicularis oculi muscle beneath the right eye. Optimised volumetric voxel-based morphometry implemented in SPM2 was used to investigate the relationship of PPI (prepulse onset-to-pulse onset interval 120msec) to regional grey matter (GM) volumes. Significant positive correlations were obtained between PPI and GM volume in the dorsolateral prefrontal, middle frontal and the orbital/medial prefrontal cortices. Our findings are consistent with (a) previous suggestions of susceptibility of PPI to cognitive processes controlled in a 'top down' manner by the cortex and (b) the hypothesis that compromised neural resources in the frontal cortex contribute to reduced PPI in schizophrenia.