Metabolic reprogramming induced by CRP deficiency or human CRP transgenic in influenza-infected mice.

INTRODUCTION

C-reactive protein (CRP) plays dual roles in influenza infection, contributing to immune protection but potentially exacerbating severe outcomes.

METHODS

Here, we investigated CRP-driven metabolic reprogramming in influenza A (H1N1)-infected mice. Metabolomic profiling was performed on lung tissues from wild-type (WT), CRP-deficient (KO), and human CRP transgenic (KI) mice. Correlations were analyzed between metabolites and immune checkpoint LAIR-1, viral load, and serum IL-17/IFN-γ levels.

RESULTS

In WT mice, H1N1 infection triggered metabolic resource redistribution, dynamic inflammatory regulation, antioxidant responses, and immune cell activation. Conversely, KI mice exhibited impaired PUFA/PLA2-mediated inflammatory control. KO mice showed hypoimmunity with premature tryptophan-kynurenine shift, glutathione and proline synthesis defects, etc. Oxidized glutathione and kynurenine correlated significantly with immune checkpoint LAIR-1, or viral TCID50.

DISCUSSION: These findings demonstrate that CRP deficiency or human CRP transgenic induces distinct metabolic reprogramming post-infection. Metabolic alterations, particularly in energy redistribution, antioxidant defense, and immune-related pathways, may serve as biomarkers for disease progression in severe influenza. The results highlighted CRP's role in balancing metabolic and immune homeostasis during viral infection.