Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity

Citation

Verified title: Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity
Publication year: 2011
DOI: 10.1038/ni.2045
Metadata source: crossref-doi (confidence: high)
Original local title: Innate lymphoid cells mediate influenza-induced airway hyper-reactivity independently of adaptive immunity

Ingest Mode

Mode: focused manual crystallization mode
Meaning: this source page has been manually upgraded for a priority crystallization pass and may support durable topic/entity/project/digest synthesis.
Required boundary: reusable claims from this source still need source-linked species, tissue, assay, model, and confidence labels.

Source Type

primary research article
mouse influenza A infection model focused on acute airway hyper-reactivity
lung ILC2-like/natural-helper-cell and IL-33/IL-13 axis paper
crystallization status: manually promoted into batch 1 high-priority lung ILC source note

Evidence Profile

Overall confidence: high for mouse influenza-induced AHR requiring innate lymphoid/natural helper cells and the IL-33/IL-13 axis.
Directness to this project: high for respiratory virus-triggered ILC2-like airway pathology; medium for modern ILC2 nomenclature because the paper uses the earlier natural-helper-cell framing.
Evidence type: mouse infection model, adaptive-immunity-deficient context, cytokine-axis perturbation, lung inflammatory physiology.
Main biological axis: influenza A -> alveolar macrophage/NLRP3-associated IL-33 -> ST2+ innate lymphoid/natural helper cells -> IL-13 -> AHR.

Why It Matters Here

This is a foundational lung ILC source for the pathogenic side of respiratory viral infection. It supports the idea that influenza can induce acute airway hyper-reactivity through an innate lymphoid IL-33/IL-13 pathway without requiring adaptive TH2 immunity.

Key Findings

Influenza A infection induced acute airway hyper-reactivity in mice independently of TH2 cells and adaptive immunity.
The response required the IL-13/IL-33 axis and a non-T/non-B innate lymphoid population described as natural helper cells.
Influenza infection increased IL-33 production by alveolar macrophage-linked pathways and activated IL-13-producing innate lymphoid cells.
The source supports a viral-triggered pathogenic ILC2-like branch rather than a general model for all asthma endotypes.

Claim-Level Confidence

High confidence: influenza A can drive acute AHR in this mouse model through innate lymphoid/natural helper cells rather than adaptive TH2 cells.
High confidence: IL-33 and IL-13 are central to the airway hyper-reactivity mechanism in this source.
Medium confidence: this source maps well onto modern lung ILC2 biology, but historical nomenclature should be preserved when making precise claims.
Low confidence: direct extension to human asthma or chronic post-viral airway disease requires additional human or translational support.

Methods and Context

Mouse influenza A infection model with airway physiology readouts.
Includes adaptive-immunity-independent framing and innate lymphoid/natural helper cell identification.
Cytokine axis centers on IL-33 and IL-13.
Best used for acute viral airway hyper-reactivity, not for repair or chronic remodeling claims.

Caveats

The paper predates current ILC2 nomenclature; retain the natural-helper-cell/ILC2-like wording when necessary.
This source emphasizes acute AHR, not epithelial repair.
Human relevance is inferential unless paired with human airway or asthma evidence.

Contradiction and Supersession

Contradiction/tension: contrasts with influenza repair literature where lung ILCs can support tissue homeostasis through amphiregulin.
Supersession status: not superseded; best interpreted as the pathogenic viral-AHR branch of lung ILC2-like biology.