Differential cytokine gene expression and secretion after phagocytosis by a human monocytic cell line of Toxoplasma gondii compared with Mycobacterium tuberculosis

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Abstract
Toxoplasma gondii mfcclion may be clinically silent in immunocompetent individuals but may cause fatal disease in immunocotripromised patients such as those with HIV infection. Proinnammatory cytokines are known to be important in murine resistance to T. gondii but there are no data from human models of infection. We have investigated whether phagocytosis of T. gondii, of Mycobactcrium tuberculosis (a pathogen which elicits a granulomatous host immune response) and of men latex particles by THP‐I celts, a human monocytic litie. caused gene expression and secretion of tumour neerosis factor (TNF), IL‐6and IL‐8. These cytokines are important in recruitment and activation of T lymphocytes, and both TNF and IL‐6 may have direct antitoxoplasmaeidal and antimycobaeterial activity. Phagocytosis of T. gondii by THP‐1 cells resulted in minimal gene expression and secretion of TNF, IL‐6 and IL‐8 similar to that following phagocytosis of inert latex particles. In contrast, phagocytosis of M. tuberculosis resulted in increased gene expression of TNF and IL‐8 as well as increased secretion of all three cytokines. particularly IL‐8. These observations may partially explain the frequency of non‐inflammatory host responses to T. gondii in immunccompetent individuals.