Role of the lung microbiome in SARS-CoV-2 infection – The effect of intranasal antibiotic treatment on the type I interferon response and microglial morphology in the CNS

Introduction Upon the infection with SARS-CoV-2, many patients not only show respiratory, but also central nervous system (CNS) symptoms. Additionally, type I interferons play an important role in the viral containment and seem to be dysregulated in some patients with COVID-19. In this study, the influence of the lung microbiome on the cytokine profile in lung and CNS of K18-hACE2 mice is investigated with special emphasis on microglia. In a second step, the effects on the susceptibility for a SARS-CoV-2-infection will be evaluated as well.

Materials and Methods In the first part of the study, K18-hACE2 mice received intranasal antibiotic treatment (neomycin and vancomycin) for 7 days to modulate the lung microbiome. Following necropsies, tissue samples are investigated pathomorphologically. The interferon response of type I/II is investigated at the cellular and molecular level using flow cytometry and quantitative PCR for lung and CNS. Lung microbiome composition is assessed by 16S rRNA sequencing of BALF and lung tissue. The next steps include SARS-CoV-2 infection of K18-hACE2 mice previously treated with antibiotics and/or probiotics, respectively.

Results Preliminary results from non-infected K18-hACE2 mice show increased expression of type I interferon-related genes in the lung and CNS as well as increased Iba-1 positivity within the CNS, respective of a changed microglial morphology.

Conclusions Intranasal treatment with neomycin might affect the interferon-response in the lung and CNS and microglial activity in the brain of K18-hACE2 mice.

 

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Artikel online veröffentlicht:
26. Juni 2024