Increased pulmonary monocyte infiltration and attenuated phagocytosis defines perinatal dysfunction of innate immunity in Cystic Fibrosis
Jaudas, F.; Bartenschlager, F.; Shashikadze, B.; Santamaria, G.; Schnell, A.; Naumann-Barsch, N.; Bruns, H.; Graeber, S. Y.; Baehr, A.; Cambra-Bort, M.; Stirm, M.; Stoeckl, J. B.; Krebs, S.; Blum, H.; Schulz, C.; Zawada, D.; Caballero-Posadas, I.; Kunzelmann, K.; Moretti, A.; Laugwitz, K.-L.; Kupatt, C.; Saalmueller, A.; Froehlich, T.; Wolf, E.; Mall, M. A.; Mundhenk, L.; Gerner, W.; Klymiuk, N.
Show abstract
In Cystic Fibrosis (CF) patients, cycles of infection and inflammation lead to fatal lung damage. While diminished mucus clearance is restored by highly effective CFTR modulator therapy, inflammation and infection persist in treated patients, suggesting alternative mechanisms may contribute to impaired immunity in CF. Here, we made use of a CF pig model to investigate the innate immune system at birth, before the onset of infection. We observed a substantial change in the composition of tissue resident immune cells towards emergency myelopoiesis, accompanied by increased infiltration of monocytes into CF lungs. A more immature status in the transcriptome profile of classical monocytes in CF pigs and preschool children with CF correlated with reduced phagocytic capacity, confirming a congenital and translationally conserved aberration of the immune system in CF. The lack of CFTR expression in circulating monocytes indicates an indirect etiology of these effects and suggests that additional immunological treatments are necessary for CF patients. One Sentence SummaryIncreased infiltration of lung tissue by monomyeloid cells and their impaired phagocytic potential cause dysfunctional imprinting of mucosal immunity in Cystic Fibrosis airways at birth and suggest early and specific treatment of the innate immune system in patients.
Matching journals
The top 7 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Diverse homeostatic and immunomodulatory roles of immune cells in the developing mouse lung revealed at single cell resolution 94%
- Tongue immune compartment analysis reveals spatial macrophage heterogeneity 94%
- Bronchus-associated macrophages are positioned for soluble antigen capture from the airway lumen and are capable of local Th2 cell activation 94%
Similar papers in this journal
- Maternal γδ T Cells Shape Offspring Pulmonary Type-2 Immunity In A Microbiota-Dependent Manner 95%
- Patient-specific iPSCs carrying an SFTPC mutation reveal the intrinsic alveolar epithelial dysfunction at the inception of interstitial lung disease 94%
- MAIT cells protect against sterile lung injury 94%
Similar papers in this journal
- Epithelial antigen presentation controls commensal-specific intraepithelial T-cells in the gut 94%
- Distinct functions of tissue-resident and circulating memory Th2 cells in allergic airway disease 94%
- Monocyte-derived macrophages aggravate pulmonary vasculitis via cGAS/STING/IFN-mediated nucleic acid sensing 94%
Similar papers in this journal
Similar papers in this journal
- Single-cell analysis of bronchoalveolar cells in inflammatory and fibrotic post-COVID lung disease 96%
- Deletion of cftr leads to an excessive neutrophilic response and defective tissue repair in a zebrafish model of sterile inflammation 93%
- Th17 immunity in the colon is controlled by two novel subsets of colon-specific mononuclear phagocytes 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.