title: Large scale comparison of innate responses to viral and bacterial pathogens in mouse and macaque.
abstract: Viral and bacterial infections of the lower respiratory tract are major causes of morbidity and mortality worldwide. Alveolar macrophages line the alveolar spaces and are the first cells of the immune system to respond to invading pathogens. To determine the similarities and differences between the responses of mice and macaques to invading pathogens we profiled alveolar macrophages from these species following infection with two viral (PR8 and Fuj/02 influenza A) and two bacterial (Mycobacterium tuberculosis and Francisella tularensis Schu S4) pathogens. Cells were collected at 6 time points following each infection and expression profiles were compared across and between species. Our analyses identified a core set of genes, activated in both species and across all pathogens that were predominantly part of the interferon response pathway. In addition, we identified similarities across species in the way innate immune cells respond to lethal versus non-lethal pathogens. On the other hand we also found several species and pathogen specific response patterns. These results provide new insights into mechanisms by which the innate immune system responds to, and interacts with, invading pathogens.
authors.affiliation: Lane Center for Computational Biology, Carnegie Mellon University, Pittsburgh, Pennsylvania, United States of America.
authors.forename: Guy
authors.initials: G
authors.lastname: Zinman
authors.forename: Rachel
authors.initials: R
authors.lastname: Brower-Sinning
authors.forename: Chineye H
authors.initials: CH
authors.lastname: Emeche
authors.forename: Jason
authors.initials: J
authors.lastname: Ernst
authors.forename: Grace Tzu-Wei
authors.initials: GT
authors.lastname: Huang
authors.forename: Shaun
authors.initials: S
authors.lastname: Mahony
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Myers
authors.forename: Dawn M
authors.initials: DM
authors.lastname: O'Dee
authors.forename: JoAnne L
authors.initials: JL
authors.lastname: Flynn
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Nau
authors.forename: Ted M
authors.initials: TM
authors.lastname: Ross
authors.forename: Russell D
authors.initials: RD
authors.lastname: Salter
authors.forename: Panayiotis V
authors.initials: PV
authors.lastname: Benos
authors.forename: Ziv
authors.initials: Z
authors.lastname: Bar Joseph
authors.forename: Penelope A
authors.initials: PA
authors.lastname: Morel
mesh_terms: D000818:Animals; D001419:Bacteria / Q000276:immunology*; D005604:Francisella tularensis / Q000276:immunology; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions / Q000235:genetics / Q000276:immunology*; D007113:Immunity, Innate / Q000235:genetics* / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology; D050839:Interferon Regulatory Factor-7 / Q000235:genetics / Q000378:metabolism; D008251:Macaca / Q000382:microbiology* / Q000821:virology*; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000382:microbiology / Q000821:virology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology; D020411:Oligonucleotide Array Sequence Analysis; D009976:Orthomyxoviridae Infections / Q000235:genetics / Q000821:virology; D015398:Signal Transduction / Q000235:genetics; D013045:Species Specificity; D014376:Tuberculosis / Q000235:genetics / Q000382:microbiology; D014406:Tularemia / Q000235:genetics / Q000382:microbiology; D015854:Up-Regulation; D014780:Viruses / Q000276:immunology*
chemical_list: D050839:Interferon Regulatory Factor-7