Generating prophylactic immunity against arboviruses in vertebrates and invertebrates

Rawle, Daniel J.; Hugo, Leon E.; Cox, Abigail L.; Devine, Gregor J.; Suhrbier, Andreas

doi:10.1038/s41577-024-01016-6

Cited by 2 publications

(1 citation statement)

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“…The concept of "protective inflammation" was recently described for COVID-19 [55] and clearly applies to many other viral infections where subclinical or mild infections are also well documented [149]. Deleterious or pathological inflammatory disease processes tend to be the focus of research, with perhaps less attention paid to characterisation of inflammatory responses that are resolved and lead to subclinical or mild disease and sequelae-free outcomes [150,151].…”

Section: Discussionmentioning

confidence: 99%

Tracking inflammation resolution signatures in lungs after SARS-CoV-2 omicron BA.1 infection of K18-hACE2 mice

Carolin,

Yan,

Bishop

et al. 2024

Preprint

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The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes Coronavirus Disease 2019 (COVID-19), which can result in severe disease often characterised by a 'cytokine storm' and the associated acute respiratory distress syndrome. However, many infections with SARS-CoV-2 are mild or asymptomatic throughout the course of infection. Although blood biomarkers of severe disease are well studied, less well understood are the inflammatory signatures in lung tissues associated with mild disease or silent infections, wherein infection and inflammation are rapidly resolved leading to sequelae-free recovery. Herein we described RNA-Seq and histological analyses of lungs over time in an omicron BA.1/K18-hACE2 mouse infection model, which displays these latter features. Although robust infection was evident at 2 days post infection (dpi), viral RNA was largely cleared by 10 dpi. Acute inflammatory signatures showed a slightly different pattern of cytokine signatures compared with severe infection models, but where much diminished 30 dpi and absent by 66 dpi. Cellular deconvolution identified significantly increased abundance scores for a number of anti-inflammatory pro-resolution cell types at 5/10 dpi. These included type II innate lymphoid cells, T regulatory cells, and interstitial macrophages. Genes whose expression trended downwards over 2 - 66 dpi included biomarkers of severe disease and were associated with 'cytokine storm' pathways. Genes whose expression trended upward during this period were associated with recovery of ciliated cells, AT2 to AT1 transition, reticular fibroblasts and innate lymphoid cells, indicating a return to homeostasis. Very few differentially expressed host genes were identified at 66 dpi, suggesting near complete recovery. The parallels between mild or subclinical infections in humans and those observed in this BA.1/K18-hACE2 mouse model are discussed.

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