We are interested in how bacteria and bacterial products shape the development of subsequent innate and adaptive immune responses with the goal of understanding how these host-microbe interactions influence pathogenesis of infections, autoimmunity, allergy, and cancer. In 2013, we have focused on host defense against the bacterial pathogen Staphylococcus aureus. These studies have uncovered the role of the IL-20 receptor in promoting S. aureus skin infection, providing insight into the regulation of key anti-staphylococcal inflammatory pathways such as IL-1 and IL-17 during infection. In addition, in 2013 we have identified the role of dietary exposures and host responses to intestinal commensals on development of IL-17-related immune responses that are relevant to susceptibility to infection and inflammatory diseases. With these studies we have enhanced our understanding of the mechanisms controlling skin and mucosal host defense and identified potential pathways that can be targeted to enhance efficacy of vaccines and therapies against cancer, infection, and immune-mediated diseases.

Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2013
Total Cost
$882,903
Indirect Cost
City
State
Country
Zip Code
Hanson, Miranda L; Hixon, Julie A; Li, Wenqing et al. (2014) Oral delivery of IL-27 recombinant bacteria attenuates immune colitis in mice. Gastroenterology 146:210-221.e13
Myles, Ian A; Pincus, Nathan B; Fontecilla, Natalia M et al. (2014) Effects of parental omega-3 fatty acid intake on offspring microbiome and immunity. PLoS One 9:e87181
Janelsins, Brian M; Lu, Mingfang; Datta, Sandip K (2014) Altered inactivation of commensal LPS due to acyloxyacyl hydrolase deficiency in colonic dendritic cells impairs mucosal Th17 immunity. Proc Natl Acad Sci U S A 111:373-8
Myles, Ian A; Fontecilla, Natalia M; Valdez, Patricia A et al. (2013) Signaling via the IL-20 receptor inhibits cutaneous production of IL-1ýý and IL-17A to promote infection with methicillin-resistant Staphylococcus aureus. Nat Immunol 14:804-11
Myles, Ian A; Fontecilla, Natalia M; Janelsins, Brian M et al. (2013) Parental dietary fat intake alters offspring microbiome and immunity. J Immunol 191:3200-9
Hayashi, Tomoko; Gray, Christine S; Chan, Michael et al. (2009) Prevention of autoimmune disease by induction of tolerance to Toll-like receptor 7. Proc Natl Acad Sci U S A 106:2764-9
del Pilar Jimenez-A, M; Viriyakosol, S; Walls, L et al. (2008) Susceptibility to Coccidioides species in C57BL/6 mice is associated with expression of a truncated splice variant of Dectin-1 (Clec7a). Genes Immun 9:338-48