CARD9 Deficiency Increases Hippocampal Injury Following Acute Neurotropic Picornavirus Infection but Does Not Affect Pathogen Elimination

Abstract

Neurotropic viruses target the brain and contribute to neurologic diseases. Caspase recruitment domain containing family member 9 (CARD9) controls protective immunity in a variety of infectious disorders. To investigate the effect of CARD9 in neurotropic virus infection, CARD9−/− and corresponding C57BL/6 wild-type control mice were infected with Theiler’s murine encephalomyelitis virus (TMEV). Brain tissue was analyzed by histology, immunohistochemistry and molecular analyses, and spleens by flow cytometry. To determine the impact of CARD9 deficiency on T cell responses in vitro, antigen presentation assays were utilized. Genetic ablation of CARD9 enhanced early pro-inflammatory cytokine responses and accelerated infiltration of T and B cells in the brain, together with a transient increase in TMEV-infected cells in the hippocampus. CARD9−/− mice showed an increased loss of neuronal nuclear protein+ mature neurons and doublecortin+ neuronal precursor cells and an increase in β-amyloid precursor protein+ damaged axons in the hippocampus. No effect of CARD9 deficiency was found on the initiation of CD8+ T cell responses by flow cytometry and co-culture experiments using virus-exposed dendritic cells or microglia-enriched glial cell mixtures, respectively. The present study indicates that CARD9 is dispensable for the initiation of early antiviral responses and TMEV elimination but may contribute to the modulation of neuroinflammation, thereby reducing hippocampal injury following neurotropic virus infection.

Infection Studies with Airway Organoids from Carollia perspicillata Indicate That the Respiratory Epithelium Is Not a Barrier for Interspecies Transmission of Influenza Viruses

“…For characterization of the bat airway, fresh bat trachea and lung from the University of Veterinary Medicine Hannover, Institute of Zoology as previously indicated were obtained separately and fixed in 10% neutral buffered formalin. As described previously ( 61 , 62 ), formalin-fixed paraffin-embedded samples were sectioned at 2-μm thickness and prepared for hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) analysis using a standard protocol. To localize the expression of different cell types in the bat airway, IHC staining of bat trachea and bat lung were performed.…”

Exploring SARS-CoV2 host-pathogen interactions and associated fungal infections cross-talk: Screening of targets and understanding pathogenesis

“…Certain articles hypothesized the role of pioglitazone (thiazolidinedione) in modulating lung injury in COVID-19 patients, which is an inhibitor of the NF-kB and MAPK pathways by reducing expression of CARD9 [13] , [72] . Though it is reported that CARD9 plays a protective role in fungal infections, it is known to play an ambivalent role in viral diseases as in cases of influenza and coxsackievirus [54] . Therefore, this dual-edge sword needs experimental investigations to understand the role of CARD9 signaling in modulating fungal infection susceptibility among COVID-19 patients.…”

Neuropathologic and molecular aspects of a canine distemper epizootic in red foxes in Germany

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