# Dendritic cell dysfunction, including impaired IL-12 production, is associated with chronic pulmonary aspergillosis

## TL;DR

The study finds that chronic pulmonary aspergillosis is linked to immune system issues, particularly in dendritic cells and monocytes, which may lead to reduced immune responses.

## Contribution

The study identifies dendritic cell dysfunction and impaired IL-12 production as key features of chronic pulmonary aspergillosis.

## Key findings

- CPA patients have reduced conventional dendritic cell subsets and impaired activation markers.
- cDC1s in CPA patients show reduced IL-12p40, TNFα, and CD86 expression.
- CPA patients with prior TB have higher frequencies of activated cDC1s.

## Abstract

Growing evidence links immune dysfunction, notably impaired IFNγ production, to chronic pulmonary aspergillosis (CPA), but understanding of the immune phenotype in CPA patients remains limited.

To investigate this, we recruited 25 CPA patients and 25 controls with bronchiectasis, isolating immune cells from peripheral blood for detailed flow cytometric phenotyping at resting state and after ex vivo stimulation with the TLR2/Dectin-1 agonist Zymosan.

CPA patients exhibited pronounced neutrophilia and a reduced frequency of conventional dendritic cell (DC) subsets at baseline compared to bronchiectasis controls. Post-stimulation, DC and monocyte subsets in CPA patients showed significantly lower expression of activation markers. Notably, cDC1s displayed reduced IL-12p40, TNFα, and CD86 expression. CPA patients with a history of tuberculosis (TB) had significantly higher frequencies of activated cDC1s. Machine learning analysis validated these immunological parameters as predictive of CPA status.

Our findings suggest that immune dysfunction in CPA involves DC and monocyte impairments, potentially contributing to IFNγ deficiency through reduced IL-12 production and co-stimulatory capacity in cDC1s. These results also hint at the presence of innate immune memory in CPA patients with prior TB. Our study advances understanding of the immune dysfunction underlying CPA.

Growing evidence links immune dysfunction, notably impaired IFNγ production, to chronic pulmonary aspergillosis (CPA), but an understanding of the immune phenotype in CPA patients remains limited. To investigate this, we recruited 25 CPA patients and 25 controls with bronchiectasis, isolating immune cells from peripheral blood for detailed flow cytometric phenotyping at resting state and after ex vivo stimulation with the TLR2/Dectin-1 agonist Zymosan. Our findings suggest that immune dysfunction in CPA involves DC and monocyte impairments, potentially contributing to IFNγ Deficiency through reduced IL-12 production and co-stimulatory capacity in cDC1s.

Graphical Abstract