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.
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.
Qiu
Liyou
L
Department of Microbiology and Immunology, University of Illinois College of Medicine, Chicago, IL, USA.
Huang
Dan
D
Chen
Cystal Y
CY
Wang
Richard
R
Shen
Ling
L
Shen
Yun
Y
Hunt
Robert
R
Estep
James
J
Haynes
Barton F
BF
Jacobs
William R
WR
Letvin
Norman
N
Du
George
G
Chen
Zheng W
ZW
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
D016207:Cytokines; D011956:Receptors, Cell Surface