Dataset Information

Non-classical tissue monocytes and two functionally distinct populations of interstitial macrophages populate the mouse lung.

ABSTRACT: Resident tissue macrophages (RTM) can fulfill various tasks during development, homeostasis, inflammation and repair. In the lung, non-alveolar RTM, called interstitial macrophages (IM), importantly contribute to tissue homeostasis but remain little characterized. Here we show, using single-cell RNA-sequencing (scRNA-seq), two phenotypically distinct subpopulations of long-lived monocyte-derived IM, i.e. CD206+ and CD206-IM, as well as a discrete population of extravasating CD64+CD16.2+ monocytes. CD206+ IM are peribronchial self-maintaining RTM that constitutively produce high levels of chemokines and immunosuppressive cytokines. Conversely, CD206-IM preferentially populate the alveolar interstitium and exhibit features of antigen-presenting cells. In addition, our data support that CD64+CD16.2+ monocytes arise from intravascular Ly-6Clo patrolling monocytes that enter the tissue at steady-state to become putative precursors of CD206-IM. This study expands our knowledge about the complexity of lung IM and reveals an ontogenic pathway for one IM subset, an important step for elaborating future macrophage-targeted therapies.

SUBMITTER: Schyns J

PROVIDER: S-EPMC6722135 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Non-classical tissue monocytes and two functionally distinct populations of interstitial macrophages populate the mouse lung.

Schyns Joey J Bai Qiang Q Ruscitti Cecilia C Radermecker Coraline C De Schepper Sebastiaan S Chakarov Svetoslav S Farnir Frédéric F Pirottin Dimitri D Ginhoux Florent F Boeckxstaens Guy G Bureau Fabrice F Marichal Thomas T

Nature communications 20190903 1

Resident tissue macrophages (RTM) can fulfill various tasks during development, homeostasis, inflammation and repair. In the lung, non-alveolar RTM, called interstitial macrophages (IM), importantly contribute to tissue homeostasis but remain little characterized. Here we show, using single-cell RNA-sequencing (scRNA-seq), two phenotypically distinct subpopulations of long-lived monocyte-derived IM, i.e. CD206<sup>+</sup> and CD206<sup>-</sup>IM, as well as a discrete population of extravasating ...[more]

PMID: 31481690

Similar Datasets

Project description:During an immune response, macrophages systematically rewire their metabolism in specific ways to support their diversve functions. However, current knowledge of macrophage metabolism is largely concentrated on central carbon metabolism. Using multi-omics analysis, we identified nucleotide metabolism as one of the most significantly rewired pathways upon classical activation. Further isotopic tracing studies revealed several major changes underlying the substantial metabolomic alterations: 1) de novo synthesis of both purines and pyrimidines is shut down at several specific steps; 2) nucleotide degradation activity to nitrogenous bases is increased but complete oxidation of bases is reduced, causing a great accumulation of nucleosides and bases; and 3) cells gradually switch to primarily relying on salvaging the nucleosides and bases for maintaining most nucleotide pools. Mechanistically, the inhibition of purine nucleotide de novo synthesis is mainly caused by nitric oxide (NO)-driven inhibition of the IMP synthesis enzyme ATIC, with NO-independent transcriptional downregulation of purine synthesis genes augmenting the effect. The inhibition of pyrimidine nucleotide de novo synthesis is driven by NO-driven inhibition of CTP synthetase (CTPS) and transcriptional downregulation of thymidylate synthase (TYMS). For the rewiring of degradation, purine nucleoside phosphorylase (PNP) and uridine phosphorylase (UPP) are transcriptionally upregulated, increasing nucleoside degradation activity. However, complete degradation of purine bases by xanthine oxidoreductase (XOR) is inhibited by NO, diverting flux into nucleotide salvage. Inhibiting the activation-induced switch from nucleotide de novo synthesis to salvage by knocking out the purine salvage enzyme hypoxanthine-guanine phosporibosyl transferase (Hprt) significantly alters the expression of genes important for activated macrophage functions, suppresses macrophage migration, and increases pyroptosis. Furthermore, knocking out Hprt or Xor increases proliferation of the intracellular parasite Toxoplasma gondii in macrophages. Together, these studies comprehensively reveal the characteristics, the key regulatory mechanisms, and the functional importance of the dynamic rewiring of nucleotide metabolism in classically activated macrophages.

Dataset Information

Non-classical tissue monocytes and two functionally distinct populations of interstitial macrophages populate the mouse lung.

Publications

Non-classical tissue monocytes and two functionally distinct populations of interstitial macrophages populate the mouse lung.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets