Severe tuberculosis induces unbalanced up-regulation of gene networks and overexpression of IL-22, MIP-1α, CCL27, IP-10, CCR4, CCR5, CXCR3, PD1, PDL2, IL-3, IFN-β, TIM1, and TLR2 but low antigen-specific cellular responses

Liyou Qiu; Dan Huang; Crystal Y. Chen; Richard Wang; Ling Shen; Yun Shen; Robert Hunt; James Estep; Barton F. Haynes; William R. Jacobs; Norman L. Letvin; George Du; Zheng W. Chen

doi:10.1086/592448

Severe tuberculosis induces unbalanced up-regulation of gene networks and overexpression of IL-22, MIP-1α, CCL27, IP-10, CCR4, CCR5, CXCR3, PD1, PDL2, IL-3, IFN-β, TIM1, and TLR2 but low antigen-specific cellular responses

Liyou Qiu, Dan Huang, Crystal Y. Chen, Richard Wang, Ling Shen, Yun Shen, Robert Hunt, James Estep, Barton F. Haynes, William R. Jacobs, Norman L. Letvin, George Du, Zheng W. Chen

Microbiology & Immunology

Research output: Contribution to journal › Article › peer-review

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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 downregulated 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-1α, IP-10, CCR4, CCR5, and CXCR3), immune dysfunctional receptors and ligands (PD1 and PDL2), and immune activation elements (IL-3, IFN-β, 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.

Original language	English (US)
Pages (from-to)	1514-1519
Number of pages	6
Journal	Journal of Infectious Diseases
Volume	198
Issue number	10
DOIs	https://doi.org/10.1086/592448
State	Published - Nov 15 2008

ASJC Scopus subject areas

Immunology and Allergy
Infectious Diseases

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Qiu, L., Huang, D., Chen, C. Y., Wang, R., Shen, L., Shen, Y., Hunt, R., Estep, J., Haynes, B. F., Jacobs, W. R., Letvin, N. L., Du, G., & Chen, Z. W. (2008). Severe tuberculosis induces unbalanced up-regulation of gene networks and overexpression of IL-22, MIP-1α, CCL27, IP-10, CCR4, CCR5, CXCR3, PD1, PDL2, IL-3, IFN-β, TIM1, and TLR2 but low antigen-specific cellular responses. Journal of Infectious Diseases, 198(10), 1514-1519. https://doi.org/10.1086/592448

Severe tuberculosis induces unbalanced up-regulation of gene networks and overexpression of IL-22, MIP-1α, CCL27, IP-10, CCR4, CCR5, CXCR3, PD1, PDL2, IL-3, IFN-β, TIM1, and TLR2 but low antigen-specific cellular responses. / Qiu, Liyou; Huang, Dan; Chen, Crystal Y. et al.
In: Journal of Infectious Diseases, Vol. 198, No. 10, 15.11.2008, p. 1514-1519.

Research output: Contribution to journal › Article › peer-review

Qiu, L, Huang, D, Chen, CY, Wang, R, Shen, L, Shen, Y, Hunt, R, Estep, J, Haynes, BF, Jacobs, WR, Letvin, NL, Du, G & Chen, ZW 2008, 'Severe tuberculosis induces unbalanced up-regulation of gene networks and overexpression of IL-22, MIP-1α, CCL27, IP-10, CCR4, CCR5, CXCR3, PD1, PDL2, IL-3, IFN-β, TIM1, and TLR2 but low antigen-specific cellular responses', Journal of Infectious Diseases, vol. 198, no. 10, pp. 1514-1519. https://doi.org/10.1086/592448

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title = "Severe tuberculosis induces unbalanced up-regulation of gene networks and overexpression of IL-22, MIP-1α, CCL27, IP-10, CCR4, CCR5, CXCR3, PD1, PDL2, IL-3, IFN-β, 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 downregulated 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-1α, IP-10, CCR4, CCR5, and CXCR3), immune dysfunctional receptors and ligands (PD1 and PDL2), and immune activation elements (IL-3, IFN-β, 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.",

author = "Liyou Qiu and Dan Huang and Chen, {Crystal Y.} and Richard Wang and Ling Shen and Yun Shen and Robert Hunt and James Estep and Haynes, {Barton F.} and Jacobs, {William R.} and Letvin, {Norman L.} and George Du and Chen, {Zheng W.}",

note = "Funding Information: Received 21 February 2008; accepted 17 April 2008; electronically published 23 September 2008. Potential conflicts of interest: none reported. Financial support: National Institutes of Health (R01 grants HL64560 and RR13601 (both to Z.W.C.).",

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doi = "10.1086/592448",

language = "English (US)",

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T1 - Severe tuberculosis induces unbalanced up-regulation of gene networks and overexpression of IL-22, MIP-1α, CCL27, IP-10, CCR4, CCR5, CXCR3, PD1, PDL2, IL-3, IFN-β, TIM1, and TLR2 but low antigen-specific cellular responses

AU - Qiu, Liyou

AU - Huang, Dan

AU - Chen, Crystal Y.

AU - Wang, Richard

AU - Shen, Ling

AU - Shen, Yun

AU - Hunt, Robert

AU - Estep, James

AU - Haynes, Barton F.

AU - Jacobs, William R.

AU - Letvin, Norman L.

AU - Du, George

AU - Chen, Zheng W.

N1 - Funding Information: Received 21 February 2008; accepted 17 April 2008; electronically published 23 September 2008. Potential conflicts of interest: none reported. Financial support: National Institutes of Health (R01 grants HL64560 and RR13601 (both to Z.W.C.).

PY - 2008/11/15

Y1 - 2008/11/15

N2 - 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 downregulated 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-1α, IP-10, CCR4, CCR5, and CXCR3), immune dysfunctional receptors and ligands (PD1 and PDL2), and immune activation elements (IL-3, IFN-β, 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.

AB - 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 downregulated 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-1α, IP-10, CCR4, CCR5, and CXCR3), immune dysfunctional receptors and ligands (PD1 and PDL2), and immune activation elements (IL-3, IFN-β, 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.

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Severe tuberculosis induces unbalanced up-regulation of gene networks and overexpression of IL-22, MIP-1α, CCL27, IP-10, CCR4, CCR5, CXCR3, PD1, PDL2, IL-3, IFN-β, TIM1, and TLR2 but low antigen-specific cellular responses

Abstract

ASJC Scopus subject areas

UN SDGs

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