Abstract
Although a defective Th1 response has been demonstrated in patients infected with Mycobacterium tuberculosis (Mtb), the mechanisms leading to this defect are not well understood. To study the immune response to Mtb infection, we stimulated PBMC from individuals with latent tuberculosis infection (LTBI) or patients with tuberculosis (TB) with the Mtb specific antigen early secretory antigenic target-6 (ESAT-6). mRNAs for a panel of cytokines were measured using quantitative real-time PCR (qPCR). PBMC from TB patients exhibited low levels of IFN-γ, IL-12α, IL-12β, and IL-23 mRNA but high levels of IL-9 mRNA. Sera from TB patients blocked the differentiation and function of dendritic cells from TST negative (TST-) donors. Exogenous IL-9 reduced IFN-γ mRNA expression in PBMC from LTBI by 30% (n = 4) and neutralization of IL-9 restored the IFN-γ mRNA expression in PBMC from TB patients by 66% (n = 8). Thus, increased expression of IL-9 may contribute to the development of TB.
Original language | English (US) |
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Pages (from-to) | 202-210 |
Number of pages | 9 |
Journal | Clinical Immunology |
Volume | 126 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2008 |
Funding
We are grateful to Colorado State University and the NIH, NIAID Contract NO 1 AI-75320, entitled “Tuberculosis Research Materials and Vaccine Testing” for providing the recombinant proteins used in this study and to the TB Clinic at the San Francisco Department of Public Health. We thank Irina Rudoy and Cynthia Merrifield for recruitment of TB patients, blood drawing and data collection, Shu-chen Lyu for technical assistance, and Gary Schoolnik and Peter Small for helpful discussions. This work was supported by grants from the National Institutes of Health (RO1 AI051356, to C.C., and RO1 AI034238 to P.C.H.).
Keywords
- Cytokines;
- Dendritic cell;
- Human
- Mycobacterium tuberculosis;
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology