title: The dual role of dendritic cells in the immune response to human immunodeficiency virus type 1 infection.
abstract: Many aspects of the complex interaction between human immunodeficiency virus type 1 (HIV-1) and the human immune system remain elusive. Our objective was to study these interactions, focusing on the specific roles of dendritic cells (DCs). DCs enhance HIV-1 infection processes as well as promote an antiviral immune response. We explored the implications of these dual roles. A mathematical model describing the dynamics of HIV-1, CD4+ and CD8+ T-cells, and DCs interacting in a human lymph node was analysed and is presented here. We have validated the behaviour of our model against non-human primate simian immunodeficiency virus experimental data and published human HIV-1 data. Our model qualitatively and quantitatively recapitulates clinical HIV-1 infection dynamics. We have performed sensitivity analyses on the model to determine which mechanisms strongly affect infection dynamics. Sensitivity analysis identifies system interactions that contribute to infection progression, including DC-related mechanisms. We have compared DC-dependent and -independent routes of CD4+ T-cell infection. The model predicted that simultaneous priming and infection of T cells by DCs drives early infection dynamics when activated T-helper cell numbers are low. Further, our model predicted that, while direct failure of DC function and an indirect failure due to loss of CD4+ T-helper cells are both significant contributors to infection dynamics, the former has a more significant impact on HIV-1 immunopathogenesis.
authors.affiliation: Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Ian B
authors.initials: IB
authors.lastname: Hogue
authors.affiliation: Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Seema H
authors.initials: SH
authors.lastname: Bajaria
authors.affiliation: Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Fallert
authors.affiliation: Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Shulin
authors.initials: S
authors.lastname: Qin
authors.affiliation: Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA.
authors.forename: Todd A
authors.initials: TA
authors.lastname: Reinhart
authors.affiliation: Department of Microbiology and Immunology, The University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Denise E
authors.initials: DE
authors.lastname: Kirschner