title: Severe tuberculosis induces unbalanced up-regulation of gene networks and overexpression of IL-22, MIP-1alpha, CCL27, IP-10, CCR4, CCR5, CXCR3, PD1, PDL2, IL-3, IFN-beta, TIM1, and TLR2 but low antigen-specific cellular responses.
abstract: The immune mechanisms by which early host-mycobacterium interaction leads to the development of severe tuberculosis (TB) remain poorly characterized in humans. Here, we demonstrate that severe TB in juvenile rhesus monkeys down-regulated many genes in the blood but up-regulated selected genes constituting gene networks of Th17 and Th1 responses, T cell activation and migration, and inflammation and chemoattractants in the pulmonary and lymphoid compartments. Overexpression (450-2740-fold) of 13 genes encoding inflammatory cytokines and receptors (IL-22, CCL27, MIP-1alpha, IP-10, CCR4, CCR5, and CXCR3), immune dysfunctional receptors and ligands (PD1 and PDL2), and immune activation elements (IL-3, IFN-beta, TIM1, and TLR2) was seen in tissues, with low antigen-specific cellular responses. Thus, severe TB in macaques features unbalanced up-regulation of immune-gene networks without proportional increases in antigen-specific cellular responses.
authors.affiliation: Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL, USA.
authors.forename: Liyou
authors.initials: L
authors.lastname: Qiu
authors.forename: Dan
authors.initials: D
authors.lastname: Huang
authors.forename: Cystal Y
authors.initials: CY
authors.lastname: Chen
authors.forename: Richard
authors.initials: R
authors.lastname: Wang
authors.forename: Ling
authors.initials: L
authors.lastname: Shen
authors.forename: Yun
authors.initials: Y
authors.lastname: Shen
authors.forename: Robert
authors.initials: R
authors.lastname: Hunt
authors.forename: James
authors.initials: J
authors.lastname: Estep
authors.forename: Barton F
authors.initials: BF
authors.lastname: Haynes
authors.forename: William R
authors.initials: WR
authors.lastname: Jacobs
authors.forename: Norman
authors.initials: N
authors.lastname: Letvin
authors.forename: George
authors.initials: G
authors.lastname: Du
authors.forename: Zheng W
authors.initials: ZW
authors.lastname: Chen
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D053263:Gene Regulatory Networks / Q000235:genetics*; D007111:Immunity, Cellular; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008168:Lung / Q000473:pathology; D008253:Macaca mulatta; D009164:Mycobacterium Infections / Q000235:genetics / Q000276:immunology*; D011956:Receptors, Cell Surface / Q000235:genetics*; D014376:Tuberculosis / Q000276:immunology* / Q000473:pathology; D015854:Up-Regulation
chemical_list: D016207:Cytokines; D011956:Receptors, Cell Surface