Mathematical modeling of Leishmania major infection
Leishmania Major (L. major) is a species of parasites that is transmitted to humans by female sand-fly bites and infects human and in general mammalian monocytes. Monocytes act as hosts to L. major but they are also the major players in clearing the infection. In an attempt to understand the mode of action of monocytes, we have developed an Ordinary Differential Equation (ODE) model where different hypotheses such as cell intrinsic or extrinsic killing as well as parasite growth inhibition can be tested. In this framework, cell intrinsic killing refers to killing of the parasite within an infected monocyte, whereas cell extrinsic killing could be mediated by a soluble substance secreted by activated monocytes independent of their infection state. Growth inhibition, finally, is the hypothesis that activated monocytes do not kill, but simply slow down parasite replication. The model is calibrated and its results are validated using cutting edge experimental methods providing not only time resolved data on parasite load in a murine infection model, but also data on various immune cell populations, their activation state, signaling events, and information on proliferation and death of the parasites. It reproduces experimentally observed patterns accurately and provides insight into the mechanisms of long-term persistence of the parasites; the inclusion of T cell responses will help to further elucidate the role of specific immunity in the disease.
Sebastian Binder, Philippe Robert (former member), Michael Meyer-Hermann
Andreas Müller (Universität Magdeburg), Pauline Formaglio (Institut Pasteur)
- Systems Immunology- Prof. Dr. Michael Meyer-Hermann
DFG - German Research Foundation