Constitutive TNF-α signaling in neonates is essential for the development of tissue-resident leukocyte profiles at barrier sites.

Newborn infants have a high disposition to develop systemic inflammatory response syndromes (SIRSs) upon inflammatory or infectious challenges. Moreover, there is a considerable trafficking of hematopoietic cells to tissues already under noninflammatory conditions. These age-specific characteristics suggest a hitherto unappreciated crucial role of the vascular endothelium during the neonatal period. Here, we demonstrate that healthy neonates showed already strong endothelial baseline activation, which was mediated by a constitutively increased production of TNF-α. In mice, pharmacological inhibition of TNF-α directly after birth prevented subsequent fatal SIRS but completely abrogated the recruitment of leukocytes to sites of infection. Importantly, in healthy neonates, blocking TNF-α at birth disrupted the physiologic leukocyte trafficking, which resulted in persistently altered leukocyte profiles at barrier sites. Collectively, these data suggest that constitutive TNF-α-mediated sterile endothelial activation in newborn infants contributes to the increased risk of developing SIRS but is needed to ensure the postnatal recruitment of leukocytes to organs and interfaces.-Bickes, M. S., Pirr, S., Heinemann, A. S., Fehlhaber, B., Halle, S., Völlger, L., Willers, M., Richter, M., Böhne, C., Albrecht, M., Langer, M., Pfeifer, S., Jonigk, D., Vieten, G., Ure, B., von Kaisenberg, C., Förster, R., von Köckritz-Blickwede, M., Hansen, G., Viemann, D. Constitutive TNF-α signaling in neonates is essential for the development of tissue-resident leukocyte profiles at barrier sites.

Bacillary angiomatosis with atypical clinical presentation in an immunocompetent patient.

Bacillary angiomatosis is a recently described infectious disease that usually affects immunosupressed hosts with a previous history of contact with cats. We report a rare case of bacillary angiomatosis in an immunocompetent 59-year-old woman with no history of previous exposure to cats, and atypical clinical features (fever and subcutaneous nodules with ulceration on the left ankle). Histopathology of the lesion showed extensive ulceration and reactive tumor-like vascular proliferation of the blood vessels with swollen endothelial cells and an inflammatory infiltrate including neutrophils and lymphocytes in the dermis and subcutis. Staining with the Warthin-Starry method demonstrated the presence of clustered bacilli located in the extracellular matrix adjacent to the proliferating endothelial cells. Diagnosis was confirmed with the detection of Bartonella spp. DNA in the affected skin and in bone marrow using polymerase chain reaction.

The nose in leprosy: immunohistology of the nasal mucosa.

A detailed study of the nose was undertaken in 40 leprosy patients with different classifications of leprosy and different durations of disease at two hospitals in Brazil. This manuscript describes the immunohistochemical data on cellular infiltrates in the nasal biopsies of those patients. It was surprising that the damage to the whole depth of the nasal mucosa, epithelium and lamina propria was considerable, as was the case in the nasal mucosa which looked relatively normal during clinical inspection. The epithelium showed large holes which looked like very extended goblet cells. Very obvious was the lack of vasoconstriction after cocaine application, and the vessels also showed a lack of staining with factor VIII, possibly indicating a disruption of the endothelium. The number of neurofilaments was extensively reduced in all leprosy groups compared to normal controls. As in the skin, an increased number of CD68+ cells was found in the lamina propria of the nasal mucosa of the lepromatous patients. Contrary to findings in the skin, in the nasal mucosa of the borderline/lepromatous patients the number of CD4+ cells was increased and the number of CD8+ cells was decreased compared to normal controls. The number of CD8+ cells tended to be more reduced when the history of leprosy was longer. It is not clear as yet whether the reduced numbers of CD8+ cells are acquired during infection or whether persons with a low number of CD8+ cells in the nose might have a higher risk of acquiring leprosy.