Divergent macrophage responses to Mycobacterium bovis among naturally exposed uninfected and infected cattle.
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.
Medical and Pharmaceutical Biotechnology, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ), Jalisco, Mexico.
Omar A
OA
Alcaraz-López
Medical and Pharmaceutical Biotechnology, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ), Jalisco, Mexico.
Cindy
C
García-Gil
Medical and Pharmaceutical Biotechnology, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ), Jalisco, Mexico.
Claudia
C
Morales-Martínez
Medical and Pharmaceutical Biotechnology, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ), Jalisco, Mexico.
Gonzalo
G
López-Rincón
Medical and Pharmaceutical Biotechnology, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ), Jalisco, Mexico.
Ciro
C
Estrada-Chávez
Research Laboratory on Bovine Tuberculosis, Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Mexico City, Mexico.
José A
JA
Gutiérrez-Pabello
Medical and Pharmaceutical Biotechnology, Centro de Investigación y Asistencia en Tecnología y Diseño del Estado de Jalisco (CIATEJ), Jalisco, Mexico.|División de Biotecnología y Salud, Tecnológico de Monterrey, Guadalajara, Mexico.
Hugo
H
Esquivel-Solís
D000818:Animals; D002417:Cattle; D002470:Cell Survival; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D018664:Interleukin-12 / Q000235:genetics / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology*; D009163:Mycobacterium bovis / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D010587:Phagocytosis; D013481:Superoxides / Q000378:metabolism; D014380:Tuberculosis, Bovine / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D018932:Chemokine CCL2; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D016753:Interleukin-10; D018664:Interleukin-12; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II