Mycobacterium fortuitum abortion in a sow.

Two aborted Chester White pig fetuses were presented to a veterinary diagnostic laboratory in Illinois. Postmortem examination identified no gross abnormalities. Histologic evaluation revealed multifocal necrosis of chorionic epithelial cells, coalescing areas of mineralization in the placenta, and focal accumulations of viable and degenerate neutrophils in the lung. Intra- and extracellular acid-fast bacilli were identified in the lesions in both the placenta and lungs. Bacterial culture of stomach contents yielded heavy growth of Mycobacterium fortuitum, a rapidly growing nontuberculous mycobacterium (NTM), which was further confirmed through whole-genome sequencing. NTM are opportunistic pathogens commonly found in the soil and in contaminated water supplies. In animals, M. fortuitum is typically introduced through cutaneous wounds leading to infections limited to the skin, with systemic infection being uncommon. To our knowledge, abortion caused by M. fortuitum has not been reported previously.

Type I interferon response drives neuroinflammation and synapse loss in Alzheimer disease.

Type I interferon (IFN) is a key cytokine that curbs viral infection and cell malignancy. Previously, we demonstrated a potent IFN immunogenicity of nucleic acid-containing (NA-containing) amyloid fibrils in the periphery. Here, we investigated whether IFN is associated with ß-amyloidosis inside the brain and contributes to neuropathology. An IFN-stimulated gene (ISG) signature was detected in the brains of multiple murine Alzheimer disease (AD) models, a phenomenon also observed in WT mouse brain challenged with generic NA-containing amyloid fibrils. In vitro, microglia innately responded to NA-containing amyloid fibrils. In AD models, activated ISG-expressing microglia exclusively surrounded NA+ amyloid ß plaques, which accumulated in an age-dependent manner. Brain administration of rIFN-ß resulted in microglial activation and complement C3-dependent synapse elimination in vivo. Conversely, selective IFN receptor blockade effectively diminished the ongoing microgliosis and synapse loss in AD models. Moreover, we detected activated ISG-expressing microglia enveloping NA-containing neuritic plaques in postmortem brains of patients with AD. Gene expression interrogation revealed that IFN pathway was grossly upregulated in clinical AD and significantly correlated with disease severity and complement activation. Therefore, IFN constitutes a pivotal element within the neuroinflammatory network of AD and critically contributes to neuropathogenic processes.