Production of granulomas in Mycoplasma bovis infection associated with meningitis-meningoencephalitis, endocarditis, and pneumonia in cattle

Abstract

Mycoplasma bovis, the most important primary pathogen in the family Mycoplasmataceae, causes pneumonia, arthritis, otitis media, and mastitis in cattle. Histopathologic pulmonary changes associated with M. bovis infection have been characterized as suppurative-to-caseonecrotic bronchopneumonia; infection in other organs has been reported in only a few studies that examined caseonecrotic endocarditis and suppurative meningitis. Granulomatous lesions associated with M. bovis infection have been reported only rarely. We studied the granulomatous inflammation associated with M. bovis infection in several organs of 21 Japanese Black cattle. M. bovis was detected by isolation and loop-mediated isothermal amplification methods; other bacteria were detected using culture on 5% blood sheep agar and a MALDI-TOF MS Biotyper. Tissues were examined by histopathology and by immunohistochemistry (IHC) using anti-M. bovis, anti-Iba1, anti-iNOS, and anti-CD204 antibodies. All 21 cases, which included 2 cases of meningitis-meningoencephalitis, 8 cases of endocarditis, and 11 cases of bronchopneumonia, had caseonecrotic granulomatous inflammation associated with M. bovis infection. The IHC for macrophages revealed a predominance of iNOS-labeled (M1) macrophages in the inner layer of the caseonecrotic granulomas associated with meningitis-meningoencephalitis, endocarditis, and bronchopneumonia in Japanese Black cattle naturally infected with M. bovis.

Keywords: Mycoplasma bovis; caseous necrosis; cattle; classical activated macrophage; granulomatous inflammation.

Figure 1.

Representative gross lesions in the brain, heart, and lung of cattle with Mycoplasma bovis infection. A. White 2.0 × 1.5 cm nodule (asterisk) on the right side of the pons. B. A caseous nodule (asterisk) on the endocardial surface of the left atrium. C. All lung lobes have diffusely distributed nodules. The cut surface of the lung has white-to-yellow caseous material in the lung parenchyma (asterisk). H = heart.

Figure 2.

Caseonecrotic granulomatous meningitis, endocarditis, and bronchopneumonia associated with Mycoplasma bovis infection. H&E. Asterisk in panels A1, B1, B2, C1, and C2 indicates the caseonecrotic core. Dotted frame in panels A1, B1, and C1 indicates the area at higher magnification in A2, B2, and C2. A1. Multifocal caseonecrotic granulomatous meningoencephalitis with 3 layers of granulomatous inflammation. A2. The core necrotic material on the left side consists of degenerate neutrophils, with neutrophil infiltration in the border. The macrophages in the inner layer, with abundant cytoplasm, surround the caseonecrotic core; an admixture of macrophages, lymphocytes, and plasma cells surrounds the outer layer on the right side. B1. Caseonecrotic granulomatous endocarditis on the endocardial surface of the left atrium. B2. The caseonecrotic core of the granulomas (lower) is surrounded by epithelioid macrophages. C1. Caseonecrotic granulomatous bronchopneumonia with epithelioid macrophages surrounding the caseous necrotic material. C2. Epithelioid macrophages surround the necrotic material, with some engulfed degenerate neutrophils (arrows).

Figure 3.

Immunohistochemistry of Mycoplasma bovis antigen distribution, including the caseonecrotic core of granulomatous inflammation. A. Meningitis. B. Endocarditis. C. Bronchopneumonia.

Figure 4.

Immunoreactivity representative of granulomatous inflammation in cases of meningitis, endocarditis, and bronchopneumonia associated with Mycoplasma bovis infection. Asterisk indicates caseonecrotic core in all panels. A1–A3. Meningitis case. A1. Iba1-labeled macrophages surround the caseonecrotic core. A2. iNOS-labeled M1 macrophages are located in the inner layer of the granuloma. A3. CD204-labeled M2 macrophages are scattered in the outer layer of the granuloma. B1–B3. Endocarditis case. B1. Iba1-labeled macrophages surround the caseonecrotic core. B2. iNOS-labeled M1 macrophages. B3. CD204-labeled M2 macrophages. C1–C3. Bronchopneumonia case. C1. Iba1-labeled macrophages surround the necrotic center. C2. iNOS-labeled epithelioid macrophages. C3. CD204-labeled M2 are scattered in the outer layer of the granuloma.