Research

Macrophages - intestine / brain

Macrophages are strategically positioned throughout the organism. As professional phagocytes, they ingest and degrade debris and foreign material, including pathogens, and orchestrate inflammatory processes. Macrophages can be generated from distinct sources: two early, currently considered transient, hematogenic waves initiated in the yolk sac that seeds tissue macrophages prenatally, and a pathway involving hematopoietic stem cells and monocytes, that persists throughout adult life. Most macrophage compartments are established prenatally, and develop independently from each other in their respective host tissue under the influence of the local microenvironment. Recent studies revealed critical contributions of tissue macrophages to organ development and homeostasis. Specific involvement of macrophages in the maintenance of the healthy balanced steady-state remains for most tissues however incompletely defined. Using the mouse as a model, we aim to define functional contributions of specific tissue macrophages to physiology and pathophysiology.

Monocytes

Monocytes are mononuclear phagocytes that circulate in the blood. One monocyte subset seems dedicated to patrol the inner vessel wall and surveille it for integrity. A second population, defined as CD14+ cells and Ly6C+ cells in man and mouse respectively, is highly dynamic and short-lived. These cells can be recruited to sites of inflammation and injury where they can give rise to monocyte-derived DC and macrophages. Differential contributions of these cells and classical tissue-resident DC and macrophages remain largely to be defined.

Dendritic cells

Classical Dendritic cells (cDC) are migratory myeloid cells with an unrivaled potential to stimulate naïve T cells. Adoptive transfer experiments have established that cDC are derived from dedicated DC precursors which differentiate in tissue context into distinct DC subsets, including XCR1+ (CD8a+) cDC and CD11b+ DC. Functional differences between these subsets remain incompletely understood, as is their relation to monocyte-derived DC that complement the cDC compartment during inflammation.