8th Annual BMRP Investigator Meeting - Abstract
Polymorphisms in Innate Immunity Genes NOD2 and ATG16L1 Affect the Response of Human Monocytes to Mycobacterium Avium Subspecies Paratuberculosis
Dylan M. Glubb1, Richard B. Gearry2,6,a, John Pearson1, Jacqui Keenan3, Judy McKenzie4, Murray L. Barclay2,6, Rebecca L. Roberts2,5 and Robert W. Bentley1,b
1Departments of Pathology, 2Medicine, 3Surgery and 4Haematology, Christchurch Hospital (Canterbury, New Zealand); 5Department of Biochemistry, University of Otago (Dunedin, New Zealand); 6Department of Gastroenterology, Christchurch Hospital (Canterbury, New Zealand)
Background: The innate immune system genes NOD2 and ATG16L1 play important roles in bacterial recognition and processing respectively, and mutations in these genes have been associated with Crohn’s disease (CD). A specific microbial cause of CD is unknown. However, Mycobacterium avium subspecies paratuberculosis (MAP), has been strongly associated with CD and is capable of intracellular growth in monocytes where it may elicit a cytokine-driven inflammatory response. To investigate the interaction between deficiencies of the innate immune system and MAP, we harvested monocytes from peripheral blood of CD patients of known genotypes of NOD2 and ATG16L1. These monocytes were challenged with MAP and subsequent bacterial persistence and cytokine responses were monitored.
Results: Monocytes carrying a NOD2 mutation were more permissive for growth of MAP than those without (p=0.045) but this had no effect on cytokine production. Mutation of the ATG16L1 gene had no effect on bacterial survival, but did increase production of cytokines IL-10 (p=0.047) and IL-6 (p=0.019).
Conclusions: Mutations in NOD2 impair elimination of MAP, whereas those in ATG16L1 significantly alter the expression profiles of pro- and anti-inflammatory cytokines after MAP challenge, but do not affect bacterial survival.
Further work is required to clarify interactions with other CD-associated bacteria.
aPrincipal Investigator; bCo-Investigator and Presenter