VSIG4-Expressing Macrophages Contribute To Anti-Parasitic And Anti-Metastatic Responses In The Peritoneal Cavity

Van Ginderachter, J. A.; Lebegge, E.; Kancheva, D.; Van Craenenbroeck, J.; Ernst, S.; Bardet, P. M. R.; Caro, A. A.; Kiss, M.; Jumapili, N. A.; Mora Barthelmess, R.; Zivalj, M.; Assaf, N.; Elkrim, Y.; Demuytere, J.; De Jonge, J.; Raes, G.; Hadadi, E.; Devoogdt, N.; Vincke, C.; Vereecke, L.; Ceelen, W.; Stijlemans, B.; Laoui, D.; Arnouk, S. M.

doi:10.1101/2024.12.23.630094

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bioRxiv · 10.1101/2024.12.23.630094

VSIG4-Expressing Macrophages Contribute To Anti-Parasitic And Anti-Metastatic Responses In The Peritoneal Cavity

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Abstract

Peritoneal tissue-resident macrophages, also referred to as large peritoneal macrophages (LPMs), play an important role as gatekeepers of peritoneal homeostasis by providing a first line of defense against pathogenic threats. About a third of the LPMs express the surface receptor V-set and Immunoglobulin domain containing 4 (VSIG4), but it is unclear to what extent these cells differ from their VSIG4-negative counterparts and perform dedicated functions. Here, we demonstrate that VSIG4+ LPMs, in contrast to VSIG4- LPMs, are in majority derived from embryonal precursors and their occurrence is to a large extent independent from sex and microbiota. Although their transcriptome and surface proteome are indistinguishable from VSIG4- LPMs at steady-state, VSIG4+ LPMs are superior in phagocytosing Gram-positive bacteria and colorectal carcinoma (CRC) cells. In-house generated anti-VSIG4 nanobody constructs that are antibody-dependent cell-mediated cytotoxicity (ADCC)-enabled allowed a selective elimination of the VSIG4+ LPM subset without affecting the overall LPM content of the peritoneal cavity. This strategy uncovered a role for VSIG4+ LPMs in lowering the first peak of parasitemia in a Trypanosoma brucei brucei infection model and in reducing the outgrowth of CRC cells in the peritoneal cavity, a prime metastatic site in CRC patients. Altogether, our data uncover a protective role for VSIG4+ LPMs in infectious and oncological diseases in the peritoneal cavity.

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Van Ginderachter, J. A., Lebegge, E., Kancheva, D., Van Craenenbroeck, J., Ernst, S., Bardet, P. M. R., Caro, A. A., Kiss, M., Jumapili, N. A., Mora Barthelmess, R., Zivalj, M., Assaf, N., Elkrim, Y., Demuytere, J., De Jonge, J., Raes, G., Hadadi, E., Devoogdt, N., Vincke, C., Vereecke, L., Ceelen, W., Stijlemans, B., Laoui, D., Arnouk, S. M.. 2024-12-24. VSIG4-Expressing Macrophages Contribute To Anti-Parasitic And Anti-Metastatic Responses In The Peritoneal Cavity. https://doi.org/10.1101/2024.12.23.630094

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