Intest Res 2018; 16(3): 426-435  https://doi.org/10.5217/ir.2018.16.3.426
Selective M1 macrophage polarization in granuloma-positive and granuloma-negative Crohn’s disease, in comparison to intestinal tuberculosis
Prasenjit Das1, Ritika Rampal2, Sonakshi Udinia3 , Tarun Kumar1, Sucharita Pilli2, Nahid Wari2, Imtiaz Khan Ahmed2, Saurabh Kedia2, Siddhartha Datta Gupta1, Dhiraj Kumar3, Vineet Ahuja2
Departments of 1Pathology and 2Gastroenterology and Human Nutritions, All India Institute of Medical Sciences, New Delhi, 3Cellular Immunology Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India
Correspondence to: Vineet Ahuja, Department of Gastroenterology, All India Institute of Medical Sciences, Room No. 3093, Third Floor, Teaching Block, New Delhi 110029, India. Tel: +91-11-26593300, Fax: +91-9810707170, E-mail: vineet.aiims@gmail.com
Co-Correspondence to Dhiraj Kumar, Cellular Immunology Group, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi 110067, India. Tel: +91-9811263541, Fax: +91-11-26742316, E-mail: dhiraj@icgeb.res.in
Received: December 3, 2017; Revised: March 15, 2018; Accepted: March 17, 2018; Published online: July 30, 2018.
© Korean Association for the Study of Intestinal Diseases. All rights reserved.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
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 M1ϕ marker) and CD163/CD68 (an M2ϕ marker), and the ratio of M1ϕ to M2ϕ 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: M1ϕ 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, M1ϕ predominance was significant (P=0.001). In iTB, the densities of M1ϕ did not differ between granuloma-positive and granuloma-negative biopsies (P=0.1). Interestingly, higher M1ϕ polarization in CD biopsies correlated with high inflammatory response exhibited by peripheral blood-derived monocytes from these patients. Conclusions: Proinflammatory M1ϕ 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.
Keywords: Crohn disease; Tuberculosis; Macrophage; M1 macrophage; M2 macrophage


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