Macrophage polarization in lymph node granulomas from cattle and pigs naturally infected with Mycobacterium tuberculosis complex

Author:

Larenas-Muñoz Fernanda1ORCID,Hamed Mohamed G.2,Ruedas-Torres Inés1,María Sánchez-Carvajal José1,Domínguez Javier3,José Pallarés Francisco1,Carrasco Librado1,Rodríguez-Gómez Irene M.1ORCID,Gómez-Laguna Jaime1

Affiliation:

1. Department of Anatomy and Comparative Pathology and Toxicology, Pathology and Immunology Group (UCO-PIG), UIC Zoonosis y Enfermedades Emergentes ENZOEM, University of Córdoba, International Excellence Agrifood Campus ‘CeiA3’, Córdoba, Spain

2. Department of Pathology and Clinical Pathology, Faculty of Veterinary Medicine, University of Sohag, Sohag, Egypt

3. Department of Biotechnology, INIA, CSIC, Madrid, Spain

Abstract

Tuberculosis in animals is caused by members of the Mycobacterium tuberculosis complex (MTC), with the tuberculous granuloma being the main characteristic lesion. The macrophage is the main cell type involved in the development of the granuloma and presents a wide plasticity ranging from polarization to classically activated or pro-inflammatory macrophages (M1) or to alternatively activated or anti-inflammatory macrophages (M2). Thus, this study aimed to analyze macrophage polarization in granulomas from cattle and pig lymph nodes naturally infected with MTC. Tuberculous granulomas were microscopically categorized into four stages and a panel of myeloid cells (CD172a/calprotectin), M1 macrophage polarization (iNOS/CD68/CD107a), and M2 macrophage polarization (Arg1/CD163) markers were analyzed by immunohistochemistry. CD172a and calprotectin followed the same kinetics, having greater expression in late-stage granulomas in pigs. iNOS and CD68 had higher expression in cattle compared with pigs, and the expression was higher in early-stage granulomas. CD107a immunolabeling was only observed in porcine granulomas, with a higher expression in stage I granulomas. Arg1+ cells were significantly higher in pigs than in cattle, particularly in late-stage granulomas. Quantitative analysis of CD163+ cells showed similar kinetics in both species with a consistent frequency of immunolabeled cells throughout the different stages of the granuloma. Our results indicate that M1 macrophage polarization prevails in cattle during early-stage granulomas (stages I and II), whereas M2 phenotype is observed in later stages. Contrary, and mainly due to the expression of Arg1, M2 macrophage polarization is predominant in pigs in all granuloma stages.

Funder

Financial support for Operational Groups of the European Innovation Partnership for Agricultural productivity and Sustainability, EIP-AGRI

agencia nacional de investigacion y desarrollo

Publisher

SAGE Publications

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