Phagocyte responses during apoptotic cell clearance in resolution of inflammation

Principal investigator: Noelia Alonso Gonzalez
Project number: CRC 1450 C02
Project term: 01/2021–12/2024

Graphical abstract
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Heterogeneous populations of tissue-resident macrophages and those recruited during inflammation develop in different organs upon acute inflammation. The aim of this project is to elucidate the specific contribution of diverse populations of macrophages to the resolution of inflammation through the phagocytosis of apoptotic cells (1). We will use two reporter mouse models bearing green fluorescent monocytes and macrophages (2), and red fluorescent neutrophils or cardiomyocytes, which will allow us to distinguish between macrophages that phagocytose neutrophils or cardiomyocytes (3).

Combining a multiscale imaging strategy (4) with high-throughput transcriptomics and metabolomics analyses (5), we expect to decode the transcriptional and metabolic pathways in macrophages that contribute to organ-specific immune responses through the phagocytosis of diverse apoptotic cellular cargos (6).


Principal investigator

Project members


The names of the principal investigators in our network have been bolded. Publications released prior to 2021, when funding for our network commenced, represent previous project-related work.


Aranda-Pardos I, Imam-Chasan A, Alonso-Gonzalez N. Studying Efferocytosis Dynamics in Tissue-Resident Macrophages Ex Vivo. Methods Mol Biol 2024;2713: 389-405. Abstract
Liebold I, Al Jawazneh A, Casar C, Lanzloth C, Leyk S, Hamley M, Wong MN, Kylies D, Grafe SK, Edenhofer I, Aranda-Pardos I, Kriwet M, Haas H, Krause J, Hadjilaou A, Schromm AB, Richardt U, Eggert P, Tappe D, Weidemann SA, Ghosh S, Krebs CF, A-Gonzalez N, Worthmann A, Lohse AW, Huber S, Rothlin CV, Puelles VG, Jacobs T, Gagliani N, Bosurgi L. Apoptotic cell identity induces distinct functional responses to IL-4 in efferocytic macrophages. Science 2024;384: eabo7027. Abstract


Nicolas-Avila JA, Lechuga-Vieco AV, Esteban-Martinez L, Sanchez-Diaz M, Diaz-Garcia E, Santiago DJ, Rubio-Ponce A, Li JLY, Balachander A, Quintana JA, Martinez-de-Mena R, Castejon-Vega B, Pun-Garcia A, Traves PG, Bonzon-Kulichenko E, Garcia-Marques F, Cusso L, A-Gonzalez N, Gonzalez-Guerra A, Roche-Molina M, Martin-Salamanca S, Crainiciuc G, Guzman G, Larrazabal J, Herrero-Galan E, Alegre-Cebollada J, Lemke G, Rothlin CV, Jimenez-Borreguero LJ, Reyes G, Castrillo A, Desco M, Munoz-Canoves P, Ibanez B, Torres M, Ng LG, Priori SG, Bueno H, Vazquez J, Cordero MD, Bernal JA, Enriquez JA, Hidalgo A. A Network of Macrophages Supports Mitochondrial Homeostasis in the Heart. Cell 2020;183: 94-109.e23. Abstract


Rauschmeier R, Gustafsson C, Reinhardt A, Alonso Gonzalez N, Tortola L, Cansever D, Subramanian S, Taneja R, Rossner MJ, Sieweke MH, Greter M, Mansson R, Busslinger M, Kreslavsky T. Bhlhe40 and Bhlhe41 transcription factors regulate alveolar macrophage self-renewal and identity. Embo J 2019;38: e101233. Abstract


A-Gonzalez N, Quintana JA, Garcia-Silva S, Mazariegos M, Gonzalez de la Aleja A, Nicolas-Avila JA, Walter W, Adrover JM, Crainiciuc G, Kuchroo VK, Rothlin CV, Peinado H, Castrillo A, Ricote M, Hidalgo A. Phagocytosis imprints heterogeneity in tissue-resident macrophages. J Exp Med 2017;214: 1281-1296. Abstract


A-Gonzalez N, Hidalgo A. Nuclear Receptors and Clearance of Apoptotic Cells: Stimulating the Macrophage's Appetite. Front Immunol 2014;5: 211. Abstract


A-Gonzalez N, Bensinger SJ, Hong C, Beceiro S, Bradley MN, Zelcer N, Deniz J, Ramirez C, Diaz M, Gallardo G, de Galarreta CR, Salazar J, Lopez F, Edwards P, Parks J, Andujar M, Tontonoz P, Castrillo A. Apoptotic cells promote their own clearance and immune tolerance through activation of the nuclear receptor LXR. Immunity 2009;31: 245-258. Abstract