Intestinal Research

Original Article

IBD

Selective M1 macrophage polarization in granuloma-positive and granuloma-negative Crohn's disease, in comparison to intestinal tuberculosis: Prasenjit Das, Ritika Rampal, Sonakshi Udinia, Tarun Kumar, Sucharita Pilli, Nahid Wari, Imtiaz Khan Ahmed, Saurabh Kedia, Siddhartha Datta Gupta, Dhiraj Kumar, Vineet Ahuja; Intest Res 2018;16(3):426-435. Published online July 27, 2018; DOI: https://doi.org/10.5217/ir.2018.16.3.426

<b>Background/Aims</b><br/>

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.

Citations

Citations to this article as recorded by

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