title: Characterization of tuberculous granulomas in different stages of progression and associated tertiary lymphoid tissue in goats experimentally infected with Mycobacterium avium subsp. hominissuis.
abstract: Oral infection of goats with Mycobacterium avium subsp. hominissuis (MAH) resulted in a large variety of granulomas in organized gut-associated lymphatic tissues and intestinal lymph nodes. To characterize the cellular composition of granulomas, CD4(+), CD8(+), γδ, B lymphocytes and plasma, CD25(+), CD68(+), MHC-II(+), Ki67(+) and endothelial cells were labeled in consecutive frozen sections by immunohistochemistry and acid fast bacilli (AFB) by Kinyoun stain. Granulomas with extensive necrosis, little mineralization and variable numbers of AFB surrounded by many CD4(+) T cells, but only few epitheloid macrophages were observed in severely sick goats at 2-3mpi. They were interpreted as exuberant immune reaction. Organized granulomas with very few AFB were seen in clinically healthy goats at 13mpi. The necrotic cores were surrounded by a zone of granulomatous infiltrate with many epitheloid macrophages and few lymphocytes. This zone was initially wide and highly vascularized and became progressively smaller. It was enclosed by an increasing layer of connective tissue. All organized granulomas were surrounded by compartimentalized tertiary lymphoid tissue. The granulomas in experimental infection of goats with MAH reflect the heterogeneity of lesions seen in mycobacterial infections of humans and ruminants and are therefore valuable for comparative research.
authors.affiliation: Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Südufer 10, 17493, Greifswald, Insel Riems, Germany. Electronic address: Jan.Schinkoethe@fli.bund.de.
authors.forename: Jan
authors.initials: J
authors.lastname: Schinköthe
authors.affiliation: Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Naumburger Str. 96a, 07743 Jena, Germany. Electronic address: Heike.Koehler@fli.bund.de.
authors.forename: Heike
authors.initials: H
authors.lastname: Köhler
authors.affiliation: Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, Naumburger Str. 96a, 07743 Jena, Germany. Electronic address: Elisabeth.Liebler-Tenorio@fli.bund.de.
authors.forename: Elisabeth M
authors.initials: EM
authors.lastname: Liebler-Tenorio
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D004195:Disease Models, Animal; D018450:Disease Progression; D006041:Goats; D006099:Granuloma / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D006801:Humans; D007150:Immunohistochemistry; D007422:Intestines / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D008214:Lymphocytes / Q000276:immunology; D008221:Lymphoid Tissue / Q000382:microbiology / Q000473:pathology*; D009162:Mycobacterium avium / Q000276:immunology*; D009336:Necrosis; D014376:Tuberculosis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*
keywords: Animal model; Goat; Granuloma; Immune response; Lymphoid tissue; Mycobacterium avium subsp. hominissuis; Non-tuberculous mycobacteria; Tuberculosis