Primary differentiated respiratory epithelial cells respond to apical measles virus infection by shedding multinucleated giant cells.

Measles virus (MeV) is highly infectious by the respiratory route and remains an important cause of childhood mortality. However, the process by which MeV infection is efficiently established in the respiratory tract is controversial with suggestions that respiratory epithelial cells are not susceptible to infection from the apical mucosal surface. Therefore, it has been hypothesized that infection is initiated in lung macrophages or dendritic cells and that epithelial infection is subsequently established through the basolateral surface by infected lymphocytes. To better understand the process of respiratory tract initiation of MeV infection, primary differentiated respiratory epithelial cell cultures were established from rhesus macaque tracheal and nasal tissues. Infection of these cultures with MeV from the apical surface was more efficient than from the basolateral surface with shedding of viable MeV-producing multinucleated giant cell (MGC) syncytia from the surface. Despite presence of MGCs and infectious virus in supernatant fluids after apical infection, infected cells were not detected in the adherent epithelial sheet and transepithelial electrical resistance was maintained. After infection from the basolateral surface, epithelial damage and large clusters of MeV-positive cells were observed. Treatment with fusion inhibitory peptides showed that MeV production after apical infection was not dependent on infection of the basolateral surface. These results are consistent with the hypothesis that MeV infection is initiated by apical infection of respiratory epithelial cells with subsequent infection of lymphoid tissue and systemic spread.

Elevated Activation of Neutrophil Toll-Like Receptors in Patients with Acute Severe Leptospirosis: An Observational Study.

Leptospirosis is the leading cause of zoonotic morbidity and mortality globally, yet little is known about the immune mechanisms that may contribute to pathogenesis and severe disease. Although neutrophils are a key component of early immune responses to infection, they have been associated with tissue damage and inflammation in some febrile infections. To assess whether neutrophils contribute to the pathogenesis observed in severe leptospirosis, we quantitated levels of neutrophil activation markers in patients with varying disease severities. Hospitalized leptospirosis patients had significantly higher levels of toll-like receptors 2 and 4 (TLR2 and TLR4, respectively) on peripheral neutrophils than healthy controls, with the highest levels detected in patients with organ dysfunction. We observed no significant differences in other neutrophil baseline activation markers (CD62L and CD11b) or activation capacity (CD62L and CD11b levels following stimulation), regardless of disease severity. Our results provide preliminary evidence supporting the hypothesis that higher initial bacterial loads or inadequate or delayed neutrophil responses, rather than TLR-driven inflammation, may drive severe disease outcomes.

Mitohormesis in Mice via Sustained Basal Activation of Mitochondrial and Antioxidant Signaling.

Transient mitochondrial stress can promote beneficial physiological responses and longevity, termed "mitohormesis." To interrogate mitohormetic pathways in mammals, we generated mice in which mitochondrial superoxide dismutase 2 (SOD2) can be knocked down in an inducible and reversible manner (iSOD2-KD mice). Depleting SOD2 only during embryonic development did not cause post-natal lethality, allowing us to probe adaptive responses to mitochondrial oxidant stress in adult mice. Liver from adapted mice had increased mitochondrial biogenesis and antioxidant gene expression and fewer reactive oxygen species. Gene expression analysis implicated non-canonical activation of the Nrf2 antioxidant and PPARγ/PGC-1α mitochondrial signaling pathways in this response. Transient SOD2 knockdown in embryonic fibroblasts from iSOD2-KD mice also resulted in adaptive mitochondrial changes, enhanced antioxidant capacity, and resistance to a subsequent oxidant challenge. We propose that mitohormesis in response to mitochondrial oxidative stress in mice involves sustained activation of mitochondrial and antioxidant signaling pathways to establish a heightened basal antioxidant state.

Contrast Enhancement of Aneurysm Sac Post-Pipeline Treatment Interpreted as Recanalization.

Multiple imaging modalities are available to evaluate aneurysms post-flow diverter (FD) placement. Though digital subtraction angiography (DSA) is the gold standard imaging modality post-FD placement, it is not perfect, and neither are other techniques, including contrast-enhanced magnetic resonance angiography (CE-MRA) and magnetic resonance imaging (MRI). We present a case of a 73-year-old woman with a right internal carotid artery (ICA) aneurysm treated with a pipeline embolization device (PED). Initial follow-up post-PED placement by three-dimensional time-of-flight (3D-TOF) MRA demonstrated aneurysm occlusion, which was confirmed by computed tomography angiography (CTA) and CE-MRA in subsequent follow-up appointments. However, repeat CE-MRA two years later suggested recanalization of the aneurysm. After discussion with neuroradiologists and follow-up with a dynamic MRA, this finding was determined to be false. These findings shed light on the potential pitfall of using CE-MRA alone or any single imaging modality in the assessment of aneurysms post-PED placement. Our case report explores various imaging modalities used in the assessment of aneurysms post-PED placement and highlights the need to use multiple techniques for an accurate assessment.