Luminal inflammation drives location and function of CD64+ macrophages

MACCIO MARETTO L, BARRIOS BE, NGO V, ROMAGNOLI P, DENNING T, CORREA SG.

Los Cocos Cordoba

Workshop; Advanced Course on Mucosal Immunology; 2018

Society for Mucosal Immunology

The intestine contains the largest pool of macrophages in the body that is strategicallylocated underneath the epitelial layer and continuously sampling the lumen. CD64 is aspecific marker used to identify murine intestinal macrophages under both steady-stateand inflammatory conditions. To evaluate if the location of CD64+ macrophages isdependent on the inflammatory environment, we studied the distribution ofCD11b+F4/80+CD64+ cells in colon of control or DSS-induced colitis C57BL/6 mice(whole mount immunofluorescence). We found that CD64+CD11b+ and CD64+ F4/80+macrophages were distributed around the crypts in the steady-state while clusters ofthese cells predominated in injured areas with marked tissue desorganization in colitismice. To address if immune complex (IC) influence the function of CD64+ cells, westudied the production of cytokines and NO using macrophages differentiated frombone marrow of WT donors after the incubation with different stimuli (LPS, Poly(A:U) and the addition of IC (OVA-antiOVA). Upon stimulation, the production of IL-10 and NO increased 8-and 3 fold, respectively. The addition of IC reduced significantly these mediators. Finally, to establish if luminal IC have a similar effect on intestinal macrophages, sorted F4/80+ cells of lamina propia from WT donors were stimulated with opsonized fecal bacteria sorted from control or DSS-treated WT mice. Fecal bacteria (IgG+IgA+) from DSS mice reduced significantly the production of IL-10 whereas triggered the highest production of NO. Together, our results suggest a dynamic balance between homeostatic and inflammatory macrophages that is critical for immune surveillance in the intestinal environment.