Year: 1989
Type: article
Abstract: Toxoplasma gondii (T. gondii) is an obligate intracellular parasite of medical and veterinary importance. Major mediators of defense to a T. gondii infection are interferon-gamma induced effector mechanisms, e.g. inducible nitric oxide synthase, immunity related GTPases and indoleamine 2,3-dioxygenase (IDO). Suppression of T cell responses – that diminish after several weeks post infection – is observed during acute toxoplasmosis as well as in other infectious diseases. IDO catalyzes the rate limiting step of the kynurenine pathway by utilizing tryptophan. Furthermore, IDO activity has been described to possess antimicrobial and immunoregulatory properties, but its role during acute toxoplasmosis and the altered T cell responsiveness is obscure. To investigate this part, WT (C57BL/6) and IDO-deficient mice were infected intraperitoneally with T. gondii ME49 tachyzoites. Parasite burden, IDO expression as well as tryptophan and kynurenine concentrations were analyzed. During murine T. gondii infection tryptophan depletion and kynurenine detection was clearly measureable. Since the role of IDO in the T cell hyporesponsiveness during acute toxoplasmosis is incompletely understood, primed and unprimed splenocytes were isolated from infected and naïve mice, respectively. Proliferative responses of the splenocytes to ex vivo mitogen stimulation were measured by detection of incorporated 3H-thymidine. Cell sorting and subsequent cell mixing experiments as well as supernatant transfer experiments were used to break down the mode of action. The observed hyporesponsiveness was independent of IDO. We suggest that the hyporesponsiveness is influenced by nitric oxide synthase and regulatory T cells.
Source: Thorax
DOI: 10.1136/thx.44.6.510
Authors: M S Rothstein, M N Zelefsky, P Q Eichacker, D J Rudolph, M H Williams
Institution: Albert Einstein College of Medicine
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W2079474245