Journal Article


Stephen V. Gordon
David E. MacHugh
Eamonn Gormley
H Martin Vordermeier
Jing Chen
Kirsten E McLoughlin
Claire Healy
Chris Pirson
John A Browne
Nicolas C Nalpas
and 2 others



gene expression regulation rna messenger cattle immunology animals genetics tuberculosis bovine microbiology mycobacterium tuberculosis virulence biosynthesis cells cultured gene expression profiling immunity innate male mycobacterium bovis macrophages alveolar pathogenicity cytokines

Innate cytokine profiling of bovine alveolar macrophages reveals commonalities and divergence in the response to Mycobacterium bovis and Mycobacterium tuberculosis infection. (2014)

Abstract Despite sharing >99.9% genome sequence similarity at the nucleotide level, Mycobacterium tuberculosis and Mycobacterium bovis-the causative agents of human and bovine tuberculosis, respectively-exhibit distinct host preferences. M. bovis can cause disease in both cattle and humans yet rarely transmits between immuno-competent human hosts, while M. tuberculosis is a highly successful pathogen of humans that does not sustain in animal populations. Based on the key role played by alveolar macrophages during mycobacterial infection, we hypothesised that the immunological and pathological differences observed in cattle infected with virulent M. bovis and M. tuberculosis may have a basis in innate immune mechanisms; these differences, in turn, would be reflected at the macrophage mRNA and protein level. To investigate this, we have analysed the transcriptional profile of innate immune genes in bovine alveolar macrophages following 24 and 48 h infection with the genome-sequenced strains, M. bovis AF2122/97 and M. tuberculosis H37Rv. A bespoke multiplex ELISA was also used to quantify corresponding cytokine secretion in supernatants from the same infected alveolar macrophages. All cytokines showed similar significant patterns of expression (i.e., up- or down-regulation) at both the mRNA and protein levels in infected macrophages relative to parallel non-infected controls at the two time points (P ≤ 0.05). However, significant upregulation and downregulation of several innate immune genes-including TLR2, FOS, PIK3IP1, CCL4, IL1B, IL6 and TNF-and the CCL-4 protein was observed in the M. bovis-infected macrophages relative to the M. tuberculosis-infected macrophages 48 h post-infection (P ≤ 0.05). These results support the hypothesis that the divergent virulence of M. bovis and M. tuberculosis in cattle has a basis in innate immune mechanisms, which may contribute to host preference within the M. tuberculosis complex of strains.
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Full list of authors on original publication

Stephen V. Gordon, David E. MacHugh, Eamonn Gormley, H Martin Vordermeier, Jing Chen, Kirsten E McLoughlin, Claire Healy, Chris Pirson, John A Browne, Nicolas C Nalpas and 2 others

Experts in our system

Stephen V. Gordon
University College Dublin
Total Publications: 40
David E. MacHugh
University College Dublin
Total Publications: 82
E Gormley
University College Dublin
Total Publications: 68
Kirsten E McLoughlin
University College Dublin
Total Publications: 3
John A Browne
University College Dublin
Total Publications: 73
Nicolas C. Nalpas
University College Dublin
Total Publications: 14