Introduction: The intestine is the largest mucosal surface constantly exposed to numerous bacteria. It contains the largest pool of macrophages, which are the first cells invading bacteria meet with. Under steady state conditions macrophages, on the one hand have high phagocytic capacity to destroy invading bacteria, and on the other hand are able to sample antigens from the lumen providing immune tolerance to commensal bacteria. When this normal state is disturbed by infection, macrophages acquire enchased pro-inflammatory properties, which results in severe inflammation.
Methods: In this study we investigated the role of mucin2 and its monosaccharides in function of intestinal macrophages using mucin2 knockout mice (Muc2-/-), the model of IBD. The research was carried out at the Center for Genetic Resources of Laboratory Animals at the ICG SB RAS (RFMEFI61914X0005 and RFMEFI62114Х0010). To evaluate number of macrophages in the colon histological methods were used. Chemokines level in the colon was determined using multiplex assay and mRNA level was analyzed using quantitative RT-PCR.
Results: We discovered that owing to lack of mucin2, mice demonstrated decrease of monosaccharide fucose in the colon. Muc2-/- mice demonstrated increase of macrophages in the colon and increased level of CCL2 compared with wild type mice. Analysis of gene expression revealed increase of Arg1 and Marco mRNA level and no changes in iNos and Mrc1. Hence, lack of mucin2 leads to polarization of macrophages function to reparative one and activation of phagocytosis. Administration of deficient monosaccharide L-fucose to the drinking water resulted in decrease of Arg1, iNos and Marco mRNA level, increase of CXCL9 and CXCL10, along with decrease of macrophages number in the colon.
Conclusion: According to our findings, L-fucose might inhibit several functions of macrophages in vivo, suggesting this monosaccharide as potential modulator of macrophages function.
The study was supported by RFBR grant 15-04-07653.