{'fraction_non_alphanumeric': 0.02268283144309738, 'fraction_numerical': 0.00664841611263199, 'mean_word_length': 5.767195767195767, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 0, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Influenza infection triggers disease in a genetic model of experimental autoimmune encephalomyelitis

Significance Peripheral infections exacerbate symptoms of many neurological diseases, including the most common autoimmune demyelinating disease of the central nervous system (CNS), multiple sclerosis (MS). We demonstrate that influenza viral infection of autoimmune-prone mice triggers clinical and histological disease. We further show that influenza infection alters the transcriptome of the central nervous system and facilitates immune cell trafficking to the brain. Finally, we identified a specific chemokine that is upregulated in the CNS during infection that is also increased in the cerebrospinal fluid of MS patients during relapse. These observations improve our understanding of how peripheral infection may act to exacerbate neurological diseases such as multiple sclerosis. Multiple sclerosis (MS) is an autoimmune disease of the central nervous system. Most MS patients experience periods of symptom exacerbation (relapses) followed by periods of partial recovery (remission). Interestingly, upper-respiratory viral infections increase the risk for relapse. Here, we used an autoimmune-prone T-cell receptor transgenic mouse (2D2) and a mouse-adapted human influenza virus to test the hypothesis that upper-respiratory viral infection can cause glial activation, promote immune cell trafficking to the CNS, and trigger disease. Specifically, we inoculated 2D2 mice with influenza A virus (Puerto Rico/8/34; PR8) and then monitored them for symptoms of inflammatory demyelination. Clinical and histological experimental autoimmune encephalomyelitis was observed in ∼29% of infected 2D2 mice. To further understand how peripheral infection could contribute to disease onset, we inoculated wild-type C57BL/6 mice and measured transcriptomic alterations occurring in the cerebellum and spinal cord and monitored immune cell surveillance of the CNS by flow cytometry. Infection caused temporal alterations in the transcriptome of both the cerebellum and spinal cord that was consistent with glial activation and increased T-cell, monocyte, and neutrophil trafficking to the brain at day 8 post infection. Finally, Cxcl5 expression was up-regulated in the brains of influenza-infected mice and was elevated in cerebrospinal fluid of MS patients during relapse compared with specimens acquired during remission. Collectively, these data identify a mechanism by which peripheral infection may exacerbate MS as well as other neurological diseases.