Mucosal immune response to persistent Mycobacterium avium ssp. Paratuberculosis (MAP) infection in bovine gut-associated lymphoid tissues

Chronic enteric Mycobacterium avium subsp. paratuberculosis (MAP) infections are endemic in cattle worldwide but disease management is thwarted by a lack of therapeutics to prevent or control infection. A better understanding of the host-pathogen interactions occurring in Peyer's patches (PP), the portal of MAP entry and site of infection, is required to develop effective vaccines. The ruminant small intestine possesses two structurally and functionally distinct PP (discrete [dPP] found in jejunum and continuous [cPP] found in ileum). Using RNA-Seq, we investigated the long-term outcome of persistent MAP infection in dPP compared to cPP in neonatal calves using surgically isolated intestinal segments containing draining mesenteric lymph nodes (MLN) and Peyer's Patches (PP). At 12 months post-infection, MAP persisted at a detectable level in cPP (n=4), but was controlled in dPP (n=5). This study demonstrates a marked regional difference in both persistence of MAP infection and the mucosal immune responses that occur in dPP and cPP following infection. Overall design: Control uninfected gut-loops were inoculated with PBS, while MAP infected tissues were inoculated with MAP gc86 Ile_LN = draining mesenteric lymph nodes from ileum Ile_PP = continuous Peyer's patches (PP) in ileum Jej_LN = draining mesenteric lymph nodes from jejunum Jej_PP = discrete Peyer's patches (PP) in jejunum