Sensing of SARS-CoV-2-infected cells by plasmacytoid dendritic cells is modulated via an interplay between CD54/ICAM-1 and CD11a/LFA-1 α <sub>L</sub> integrin
Bibliographic record
Abstract
SARS-CoV-2 infection induces interferon (IFN) response by plasmacytoid dendritic cells (pDCs), but the underlying mechanisms are poorly defined. Here, we show that the bulk of the IFN-I release comes from pDC sensing of infected cells and not cell-free virions. Physical contact (or conjugates) between pDCs and infected cells is mediated through CD54-CD11a engagement, and such conjugate formation is required for efficient IFN-I production. Interestingly, CD11a is inducible on infected epithelial cells when they are co-cultured with PBMCs, thus allowing for potentially bidirectional cross-talks between CD54 and CD11a, which further amplify the sensing. SARS-CoV-2 variants of concern (VOCs) are sensed less efficiently than the Wuhan ancestral strain (LSPQ1), but the mechanisms driving the defect are different among the VOCs. CD11a induction on infected cells is correlated with their ability to form cell conjugates with pDCs. Impaired sensing of the Alpha variant is linked to reduced CD11a induction on infected cells and to fewer conjugates formed with pDCs. Collectively, our findings provide new insights into how SARS-CoV-2-infected cells are sensed by pDCs and reveal that this process is targeted by some VOCs to limit IFN-I production. IMPORTANCE: Type I interferons (IFN-I) represent an important component of the host's innate defense against initial SARS-CoV-2 infections. Plasmacytoid dendritic cells (pDCs) produce large quantities of IFN-I upon recognition of viral particles or infected cells. This study shows that pDCs sense infected cells more efficiently than viral particles, leading to a higher production of IFN-I. Physical contact between a pDC and an infected cell is critical to this process; the interaction is mediated via CD11a and ICAM-1 complex and potentially is bidirectional. SARS-CoV-2 variants of concern (VOCs) have evolved to limit the IFN response through different mechanisms. For the Alpha variant, reduced level of CD11a on infected cells is linked to less contact with pDCs and decreased IFN-I release. Overall, our study characterizes some of the early steps involved in pDC-mediated response against SARS-CoV-2 infection and shows that these processes are targeted by VOCs to likely limit IFN-I response and enhance viral spread.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".