IL-9 is associated with an impaired Th1 immune response in patients with tuberculosis

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.