Proceedings of the 10th International Colloquium on Paratuberculosis

Host Response and Immunology Keynote Lecture
Unraveling <strong>the</strong> Host Response to Mycobacterium avium subsp. paratuberculosis:
One Thread at a Time
Judith R. Stabel
National Animal Disease Center, USDA-ARS, Ames, Iowa, USA
The study <strong>of</strong> host immune responses to Mycobacterium avium subsp. paratuberculosis (MAP) is complicated
by a number <strong>of</strong> factors, including <strong>the</strong> protracted nature <strong>of</strong> <strong>the</strong> disease and <strong>the</strong> stealthy nature <strong>of</strong> <strong>the</strong> pathogen.
Improved tools for <strong>the</strong> measurement <strong>of</strong> immunologic responses in ruminant species, particularly <strong>the</strong> bovine,
a key target species for MAP infection, has allowed <strong>the</strong> dissection <strong>of</strong> host immunologic responses to infection
to some extent. Noted as one <strong>of</strong> <strong>the</strong> more fastidious mycobacteria, infection with MAP is <strong>of</strong>ten characterized
by periods <strong>of</strong> subclinical infection extending for 3 to 5 years. Many animals will clear <strong>the</strong> infection during this
period but it is almost impossible to distinguish by current methods animals that have cleared <strong>the</strong> infection from
those that remain infected but are able to control <strong>the</strong> progression <strong>of</strong> disease. Escalation <strong>of</strong> paratuberculosis to
a more clinical state, marked by diarrhea and weight loss, is thought be caused by immune dysfunction. Due
to <strong>the</strong> intracellular nature <strong>of</strong> MAP, <strong>the</strong> macrophage is <strong>the</strong> first defense against infection. However, MAP is able
to disarm host defense mechanisms and survive within cells <strong>of</strong> key target tissues. This disarmament is likely
due to <strong>the</strong> provocation <strong>of</strong> immune mediators that may be immunosuppressive in nature. Cytokines such as IL-
10 and TGF- β have been shown to mediate immunosuppression due to <strong>the</strong>ir inhibitory effects on CD4+ T cell
activation and IFN- γ production. However, <strong>the</strong> dynamic between macrophages (APCs), T cells, and potentially
B cells cannot be so easily explained, as a multifactorial dysregulation <strong>of</strong> host immunity is likely.
115