Selective M1 macrophage polarization in granuloma-positive and granuloma-negative Crohn's disease, in comparison to intestinal tuberculosis

BACKGROUND/AIMS: Classical M1 macrophage activation exhibits an inflammatory phenotype while alternative M2 macrophage activation exhibits an anti-inflammatory phenotype. We aimed to determine whether there are discriminant patterns of macrophage polarization in Crohn's disease (CD) and intestinal tuberculosis (iTB). METHODS: Colonic mucosal biopsies from 29 patients with iTB, 50 with CD, and 19 controls were examined. Dual colored immunohistochemistry was performed for iNOS/CD68 (an M1(φ) marker) and CD163/CD68 (an M2(φ) marker), and the ratio of M1(φ) to M2(φ) was assessed. To establish the innate nature of macrophage polarization, we analyzed the extent of mitochondrial depolarization, a key marker of inflammatory responses, in monocyte-derived macrophages obtained from CD and iTB patients, following interferon-γ treatment. RESULTS: M1(φ) polarization was more prominent in CD biopsies (P=0.002) than in iTB (P=0.2) and control biopsies. In granuloma-positive biopsies, including those in CD, M1(φ) predominance was significant (P=0.001). In iTB, the densities of M1(φ) did not differ between granuloma-positive and granuloma-negative biopsies (P=0.1). Interestingly, higher M1(φ) polarization in CD biopsies correlated with high inflammatory response exhibited by peripheral blood-derived monocytes from these patients. CONCLUSIONS: Proinflammatory M1(φ) polarization was more common in colonic mucosa of CD patients, especially in the presence of mucosal granulomas. Further characterization of the innate immune system could help in clarifying the pathology of iTB and CD.