Divergent macrophage responses to Mycobacterium bovis among naturally exposed uninfected and infected cattle

• Published in: Immunology and cell biology Vol. 95; no. 5; pp. 436 - 442
• Main Authors: Alcaraz‐López, Omar A, García‐Gil, Cindy, Morales‐Martínez, Claudia, López‐Rincón, Gonzalo, Estrada‐Chávez, Ciro, Gutiérrez‐Pabello, José A, Esquivel‐Solís, Hugo
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01-05-2017; Blackwell Science Ltd
• Subjects: Animals; Cattle; Cell Survival; Chemokine CCL2 - genetics; Chemokine CCL2 - metabolism; Female; Gene Expression Regulation; Interleukin-10 - genetics; Interleukin-10 - metabolism; Interleukin-12 - genetics; Interleukin-12 - metabolism; Macrophages - immunology; Macrophages - microbiology; Mycobacterium bovis; Mycobacterium bovis - physiology; Nitric Oxide - metabolism; Nitric Oxide Synthase Type II - genetics; Nitric Oxide Synthase Type II - metabolism; Phagocytosis; Superoxides - metabolism; Tuberculosis, Bovine - genetics; Tuberculosis, Bovine - immunology; Tuberculosis, Bovine - microbiology; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - metabolism
• ISSN: 0818-9641; 1440-1711
• DOI: 10.1038/icb.2016.114

Mycobacterium bovis, the causative agent of bovine tuberculosis (TB), is a successful pathogen that remains an important global threat to livestock. Cattle naturally exposed to M. bovis normally become reactive to the M. bovis‐purified protein derivative (tuberculin) skin test; however, some individuals remain negative, suggesting that they may be resistant to infection. To better understand host innate resistance to infection, 26 cattle from herds with a long history of high TB prevalence were included in this study. We investigated the bactericidal activity, the production of reactive oxygen and nitrogen species and the TB‐related gene expression profile after in vitro M. bovis challenge of monocyte‐derived macrophages from cattle with TB (n=17) and from non‐infected, exposed cattle (in‐contacts, n=9). The disease status was established based on the tuberculin skin test and blood interferon‐gamma test responses, the presence of visible lesions at inspection on abattoirs and the histopathology and culture of M. bovis. Although macrophages from TB‐infected cattle enabled M. bovis replication, macrophages from healthy, exposed cattle had twofold lower bacterial loads, overproduced nitric oxide and had lower interleukin (IL)‐10 gene expression (P⩽0.05). Higher mRNA expression levels of inducible nitric oxide synthase, C‐C motif chemokine ligand 2 and IL‐12 were observed in macrophages from all in‐contact cattle than in macrophages from their TB‐infected counterparts, which expressed more tumour necrosis factor‐α; however, the differences were not statistically significant owing to individual variation. These results confirm that macrophage bactericidal responses have a crucial role in innate resistance to M. bovis infection in cattle.