CXCR3⁺ effector regulatory T cells associate with disease tolerance during lower respiratory pneumovirus infection

Area of Science:

• Immunology
• Microbiome research
• Nutritional science

Background:

• Lifestyle factors like maternal diet and antibiotic use disrupt infant microbiome assembly.
• This disruption increases the risk of severe lower respiratory infections (sLRI) in infants.
• Previous studies linked maternal low-fiber diet (LFD) to exacerbated LRI severity by impairing plasmacytoid dendritic cell (pDC) recruitment and regulatory T cell (Treg) expansion.

Purpose of the Study:

• To investigate how maternal dietary fiber intake influences Treg cell phenotypes in the mediastinal lymph nodes (mLN) and lungs of neonatal mice infected with pneumonia virus of mice (PVM).

Main Methods:

• High-dimensional flow cytometry was used to analyze Treg cell populations in the lungs and mLN of PVM-infected neonatal mice.
• Mice were reared on either a low-fiber diet (LFD) or a high-fiber diet (HFD).
• pDC depletion and anti-CXCR3 treatment were employed to assess the role of specific cellular pathways.

Main Results:

• Distinct Treg cell clusters were identified in the lungs and mLN, with greater effector Treg accumulation in the lungs.
• LFD-reared pups showed decreased frequencies of various effector Treg subsets in the lungs compared to HFD-reared pups.
• Recruitment of CXCR3+ Treg cells was attenuated in LFD-reared pups, correlating with lower lung CXCL9 and CXCL10 expression. This impairment was also observed in pDC-depleted mice and after anti-CXCR3 treatment, leading to increased lung immunopathology.

Conclusions:

• PVM infection induces sequential recruitment and expansion of distinct Treg cell subsets in the lungs and mLN.
• Attenuated recruitment of CXCR3+ Treg cells in LFD-reared pups contributes to increased LRI severity.
• Strategies enhancing pDCs or CXCL9/CXCL10 expression may mitigate immune-mediated pathogenesis in severe respiratory infections.