Macrophage development in mycobacterial tissue infections

• Applicant: Professor Dr. Philipp Henneke
• Subject Area: Immunology ; Medical Microbiology and Mycology, Hygiene, Molecular Infection Biology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 545358460

The central hypothesis underlying this proposal states that plasticity of liver macrophage subsets contributes to tissue-specific mycobacterial immunity. Plasticity involves both single macrophage adaptability, as well as dynamic changes in macrophage diversity, which in turn are influenced by cellular origin and heterocellular cues from the liver microenvironment. Our preliminary data highlight temporal and spatial flexibility of Kupffer cells, the most highly differentiated liver macrophage type, in mycobacterial infection. This is directly linked to granuloma formation and modulation by acutely differentiating macrophages derived from definitive hematopoiesis. In order to break new ground, we aim here to combine high dimensional transcriptional, including epigenetic analysis with cellular immunotyping, fate-mapping and high-resolution imaging for deciphering mechanisms leading to Kupffer cell transformation in mycobacterial infection and the consequences thereof. Moreover, the role of monocytes and their progenitors in liver granuloma formation and mycobacterial immunity will be addressed. Exploring the contribution of Mφ origin and plasticity to tissue immunity against mycobacteria is of immediate translational importance, since discriminable macrophage and monocyte subsets may be targeted for adjunctive anti-mycobacterial therapy.

• DFG Programme: Research Grants