title: The role of indoleamine 2,3-dioxygenase in LP-BPM5 murine retroviral disease progression.
abstract: BACKGROUND
  Indoleamine 2,3-dioxygenase (IDO) is an immunomodulatory intracellular enzyme involved in tryptophan degradation. IDO is induced during cancer and microbial infections by cytokines, ligation of co-stimulatory molecules and/or activation of pattern recognition receptors, ultimately leading to modulation of the immune response. LP-BM5 murine retroviral infection induces murine AIDS (MAIDS), which is characterized by profound and broad immunosuppression of T- and B-cell responses. Our lab has previously described multiple mechanisms regulating the development of immunodeficiency of LP-BM5-induced disease, including Programmed Death 1 (PD-1), IL-10, and T-regulatory (Treg) cells. Immunosuppressive roles of IDO have been demonstrated in other retroviral models, suggesting a possible role for IDO during LP-BM5-induced retroviral disease progression and/or development of viral load.
  
  
  METHODS
  Mice deficient in IDO (B6.IDO-/-) and wildtype C57BL/6 (B6) mice were infected with LP-BM5 murine retrovirus. MAIDS and LP-BM5 viral load were assessed at termination.
  
  
  RESULTS
  As expected, IDO was un-inducible in B6.IDO-/- during LP-BM5 infection. B6.IDO-/- mice infected with LP-BM5 retrovirus succumbed to MAIDS as indicated by splenomegaly, serum hyper IgG2a and IgM, decreased responsiveness to B- and T-cell mitogens, conversion of a proportion of CD4+ T cells from Thy1.2+ to Thy1.2-, and increased percentages of CD11b+Gr-1+ cells. LP-BM5 infected B6.IDO-/- mice also demonstrated the development of roughly equivalent disease kinetics as compared to infected B6 mice. Splenic viral loads of B6 and B6.IDO-/- mice were also equivalent after infection as measured by LP-BM5-specific Def Gag and Eco Gag viral mRNA, determined by qRT-PCR.
  
  
  CONCLUSIONS
  Collectively, these results demonstrate IDO neither plays an essential role, nor is required, in LP-BM5-induced disease progression or LP-BM5 viral load.
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire 03756, USA.
authors.forename: Megan A
authors.initials: MA
authors.lastname: O'Connor
authors.forename: William R
authors.initials: WR
authors.lastname: Green
mesh_terms: D000818:Animals; D018450:Disease Progression; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016183:Murine Acquired Immunodeficiency Syndrome / Q000473:pathology*; D012190:Retroviridae / Q000302:isolation & purification*; D019562:Viral Load
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase