The immune system has evolved to prevent infectious diseases.  Paradoxically, genetic variation that confers resistance to certain pathogens may increase one’s risk for developing autoimmune disease, such as type 1 diabetes (T1D).  Moreover, certain infections have been implicated in either causing or preventing autoimmune disease.  Investigating this dichotomy in humans is difficult.  Instead, the nonobese diabetic (NOD) mouse is a unique inbred strain that has been used for investigating the contribution of genetic variation to T1D susceptibility and bacterial resistance, as well as determining how infection alters T1D pathogenesis.  We have identified and localised a T1D susceptibility locus, termed Idd14, on mouse chromosome 13 (Chr13).  Intriguingly, Idd14 overlaps a bacterial resistance locus, termed Listr2, identified in mice infected with Listeria monocytogenes (Listeria), a Gram-positive intracellular bacterium that causes food poisoning.  NOD mice are more susceptible to Listeria infection and have a delayed immunological response compared to C57BL/6 (B6) mice.  In contrast, congenic NOD mice, which harbour a B6-derived Chr13 interval on the NOD genetic background, exhibit resistance against Listeria infection.  These congenic mice also exhibit an increased T1D incidence.  These results suggest that B6 mice harbour genetic variation on Chr13 that increases resistance to Listeria, but may in turn increase susceptibility to autoimmune diabetes.  Ongoing studies are underway to localise these two disease loci using new congenic mouse strains, identify immunological abnormalities associated with these loci, and determine if Listeria infection alters T1D pathogenesis in NOD mice.  This research was supported by The Juvenile Diabetes Research Foundation and The USA National Institute of Diabetes and Digestive and Kidney Diseases.