Proceedings of the 10th International Colloquium on Paratuberculosis

Host Response and Immunology Perspectives Lecture
Perspectives in Host Reponse and Immunology
Kris Huygen
Scientific Institute <strong>of</strong> Public Health-ex-Pasteur Institute, Brussels, Belgium
A wide range <strong>of</strong> topics will be covered in this session:
-humoral and cellular immune responses in cattle, sheep and goats and variations in this response linked to
genetic susceptibility, age and polymorphism <strong>of</strong> <strong>the</strong> MAP isolates
-possible link <strong>of</strong> MAP infection with Crohn’s disease
-development <strong>of</strong> new or optimization <strong>of</strong> existing experimental infection models
-discovery <strong>of</strong> new antigens
-development <strong>of</strong> new vaccines based on live attenuated whole bacteria or on sub-unit components (protein and
DNA)
The interaction between <strong>the</strong> early, innate immune response and <strong>the</strong> cognate acquired immune response had not
been studied in much detail so far for infections with M. avium subsp paratuberculosis. More and more results
now suggest that a malfunctioning innate response, caused by an immature system in young animals and/or by
genetic factors (a.o. deficient reactivity to mycobacterial peptidoglycan as observed in Crohn’s patients) would
lie at <strong>the</strong> basis <strong>of</strong> <strong>the</strong> deficient cell mediated immune (CMI) response observed in animals with multibacillary
forms <strong>of</strong> <strong>the</strong> disease. The evidence for a role <strong>of</strong> Th2 and regulatory T cells in <strong>the</strong> decreased CMI responses, so
characteristic <strong>of</strong> <strong>the</strong> clinical phase <strong>of</strong> Johne’s disease, is questioned and although high levels <strong>of</strong> IL-10 can be
detected, it are CD14+ MHC class II+ monocytes ra<strong>the</strong>r than T cells that produce this cytokine and moreover,
even at early stages <strong>of</strong> infection IL-10. On <strong>the</strong> o<strong>the</strong>r hand, <strong>the</strong> role <strong>of</strong> ano<strong>the</strong>r Th subset, i.e. Th17 may be more
relevant, as gene expression <strong>of</strong> interleukin17 and interleukin 23 was found to be upregulated in an experimental
infection model <strong>of</strong> red deer during disease progression. This Th17 population has also been incriminated in
Crohn’s disease and o<strong>the</strong>r auto-immune diseases.
With respect to vaccination, it is clear that live attenuated vaccines can be very effective, but a balance has to be
found between <strong>the</strong>ir immunogenicity (less attenuated strains may be more immunogenic but may interfere with
<strong>the</strong> immunodiagnostic tests) and <strong>the</strong>ir vaccine potential. Even for subunit vaccines <strong>the</strong> interference with existing
diagnostics may be an issue. Characterization <strong>of</strong> immunodominant and specific antigens <strong>of</strong> MAP will be essential
to overcome this hurdle.
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