Microplastics dysregulate innate immunity in the SARS-CoV-2 infected lung

Bishop, Cameron R.; Yan, Kexin; Nguyen, Wilson; Rawle, Daniel J.; Tang, Bing; Larcher, Thibaut; Suhrbier, Andreas

doi:10.3389/fimmu.2024.1382655

Cited by 6 publications

(13 citation statements)

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“…Pleiotropic outcomes of SARS-CoV-2 infections in iron deficient and iron overloaded mice might be envisaged, given the complexity of iron regulation [20], the modulation of iron biomarkers and homeostasis during SARS-CoV-2 infections [14,[23][24][25][26][27][28][29][30][31], and the robust proinflammatory responses associated with SARS-CoV-2 infections [66,68,116,161]. However, perhaps unexpected was the increase in Th1/Th2 ratios and B cell signatures in both iron deficient and iron load mice.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, expression of 18 heat shock protein mRNAs was lower (Fig. 3b, DEGs), with Hspa1a and Hspa1b (Hsp70 family members) [66] the most down-regulated DEGs (Supplementary Table 2).…”

Section: Iron Deficient Vs Control Diet; Lung Rna-seq At 2 Dpimentioning

confidence: 99%

“…Differentially expressed genes were identified using EdgeR using a FDR cut-off of 0.05. Pathway analyses were performed using host DEGs and Ingenuity Pathway Analysis (IPA, v84978992) (QIAGEN), which provides Canonical pathways, Up-Stream Regulators (USR) and Diseases or Functions features as described [66,72]. Annotations without z scores or with significance (q or p) below 0.05 were removed.…”

Section: Rna-seq and Bioinformaticsmentioning

confidence: 99%

“…Here we use adult wild-type C57BL/6J mice and established models of diet-induced iron deficiency and iron overload [61][62][63][64], and SARS-CoV-2 infection [65,66]. Iron deficient and iron loaded mice were compared with control mice (fed a normal iron diet) after infection with a primary human omicron XBB isolate of SARS-CoV-2 [67].…”

Section: Introductionmentioning

confidence: 99%

“…Iron deficient and iron loaded mice were compared with control mice (fed a normal iron diet) after infection with a primary human omicron XBB isolate of SARS-CoV-2 [67]. The impacts of these diets on viral replication and inflammatory disease in the infected lung were characterized using histology (H&E staining), immunohistochemistry and RNA-Seq at 2 days post infection (dpi) (peak viral load) and 6 dpi (peak of acute immune pathology) [65, 66]. Although widespread modulations in transcriptional signatures associated with inflammatory responses were observed, neither iron deficiency nor iron overload resulted in significant increases in viral replication or histopathology.…”

Section: Introductionmentioning

confidence: 99%

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The effects of iron deficient and high iron diets on SARS-CoV-2 lung infection and disease

Carolin,

Frazer,

Yan

et al. 2024

Preprint

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The severity of Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often dictated by a range of comorbidities. A considerable literature suggests iron deficiency and iron overload may contribute to increased infection, inflammation and disease severity, although direct causal relationships have been difficult to establish. Here we generate iron deficient and iron loaded C57BL/6J mice by feeding low and high iron diets, with mice on a normal iron diet representing controls. All mice were infected with a primary omicron XXB SARS-CoV-2 isolate and lung inflammatory responses were analyzed by histology, immunohistochemistry and RNA-Seq. Compared with controls, iron deficient mice showed no significant changes in lung viral loads or histopathology, whereas, iron loaded mice showed slightly, but significantly, reduced lung viral loads and histopathology. Transcriptional changes were modest, but illustrated widespread dysregulation of inflammation signatures for both iron deficient vs. controls, and iron loaded vs. controls. Some of these changes could be associated with detrimental outcomes, whereas others would be viewed as beneficial. Diet-associated iron deficiency or overload thus induced modest modulations of inflammatory signatures, but no significant histopathologically detectable disease exacerbations.Author summaryA diet deficient in iron can lead to anemia, a widespread problem worldwide. A diet with excessive iron is less common, but can be associated with excessive consumption of iron supplements. We investigate herein using a mouse model, whether low or high iron diets predispose to detrimental outcomes in the lungs after infection with SARS-CoV-2. A considerable literature suggests iron dysregulation would promote infection and inflammation. However, we found, although inflammatory responses showed modest modulations, viral loads were unaffected or slightly reduced, and lung histopathology was either unaffected or indicated slightly less severe disease. These findings do not support a view that low or high iron diets represent comorbidities predisposing to overt detrimental outcomes for acute COVID-19 lung disease.

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Section: Discussionmentioning

confidence: 99%

“…In addition, expression of 18 heat shock protein mRNAs was lower (Fig. 3b, DEGs), with Hspa1a and Hspa1b (Hsp70 family members) [66] the most down-regulated DEGs (Supplementary Table 2).…”

Section: Iron Deficient Vs Control Diet; Lung Rna-seq At 2 Dpimentioning

confidence: 99%

Section: Rna-seq and Bioinformaticsmentioning

confidence: 99%