VSIG4‐Expressing Macrophages Contribute to Antiparasitic and Antimetastatic Responses in the Peritoneal Cavity. [[{“value”:”Els Lebegge, Daliya Kancheva, Jolien Van Craenenbroeck, Sam Ernst, Pauline M. R. Bardet, Aarushi A. Caro, Máté Kiss, Neema Ahishakiye Jumapili, Romina Mora Barthelmess, Maida Zivalj, Naela Assaf, Leen Ali, Yvon Elkrim, Jesse Demuytere, Jan De Jonge, Geert Raes, Eva Hadadi, Nick Devoogdt, Cécile Vincke, Kiavash Mohavedi, Lars Vereecke, Wim Ceelen, Benoit Stijlemans, Damya Laoui, Sana M. Arnouk, Jo A. Van Ginderachter”}]]

Although VSIG4⁺ LPMs and VSIG4⁻ LPMs are identical at the transcriptomic and surface proteomic level, VSIG4⁺ LPMs are superior phagocytes that protect against CRC peritoneal outgrowth and influence the early phase of T. brucei brucei infection.

ABSTRACT

Large peritoneal macrophages (LPMs) play a role as gatekeepers of peritoneal homeostasis by providing a first line of defense against pathogens. A third of the LPMs express the surface receptor VSIG4, but it is unclear whether these cells differ from their VSIG4-negative counterparts and perform dedicated functions. We demonstrate that VSIG4⁺, but not VSIG4⁻, LPMs are in the majority derived from embryonal precursors, and their occurrence is largely independent of sex and microbiota but increases with age. Although their transcriptome and surface proteome are indistinguishable from VSIG4⁻ LPMs at steady-state, VSIG4⁺ LPMs are superior in phagocytosing S. aureus bioparticles and colorectal carcinoma (CRC) cells. Anti-VSIG4 nanobody constructs that are ADCC-enabled allowed a selective elimination of the VSIG4⁺ LPM subset without affecting overall LPM abundance. 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 CRC outgrowth 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.