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Mycobacterium bovis  is the causative agent of bovine tuberculosis (TB), a cattle disease of global importance.  M .  bovis  infects bovine macrophages (Mø) and subverts the host cell response to generate a suitable niche for survival and replication. We investigated the role of the anti-inflammatory cytokine interleukin (IL) 10 during  in vitro  infection of bovine monocyte-derived Mø (bMDM) with two divergent UK strains of  M .  bovis , which differentially modulate expression of IL10. The use of IL10-targeting siRNA revealed that IL10 inhibited the production of IL1B, IL6, tumour necrosis factor (TNF) and interferon gamma (IFNG) during infection of bMDM with the  M .  bovis  strain G18. In contrast, IL10 only regulated a subset of these genes; TNF and IFNG, during infection with the  M .  bovis  reference strain AF2122/97. Furthermore, nitric oxide (NO) production was modulated by IL10 during AF2122/97 infection, but not at the nitric oxide synthase 2 (NOS2) mRNA level, as observed during G18 infection. However, IL10 was found to promote survival of both  M .  bovis  strains during early bMDM infection, but this effect disappeared after 24 h. The role of IL10-induced modulation of TNF, IFNG and NO production in  M .  bovis  survival was investigated using siRNA targeting TNF, IFNG receptor 1 (IFNGR1) and NOS2. Knock-down of these genes individually did not promote survival of either  M .  bovis  strain and therefore modulation of these genes does not account for the effect of IL10 on  M .  bovis  survival. However, TNF knock-down was found to be detrimental to the survival of the  M .  bovis  strain G18 during early infection. The results provide further evidence for the importance of IL10 during  M .  bovis  infection of Mø. Furthermore, they highlight  M .  bovis  strain specific differences in the interaction with the infected bMDM, which may influence the course of infection and progression of bovine TB.

plos one

Interleukin 10 knock-down in bovine monocyte-derived macrophages has distinct effects during infection with two divergent strains of Mycobacterium bovis