Dynamic interaction between Leishmania infection in mice and Th1-type CD4+ T-cells: complexity in outcome without a requirement for Th2-type responses.
The interaction between Leishmania parasites and Th1 cells is investigated using a simple mathematical model of immunological responses and parasite population growth within the host. The model generates patterns of resistance and susceptibility to infection that mirror observed trends in experimental infections of mice and of humans exposed to infection in areas of endemic transmission. The heterogeneity in outcome predicted by the model can arise either through differences in the values of the parameters that characterize the genetic background of the host or as a consequence of differences in the size of the infecting inoculum of the parasite. Detailed analyses of equilibrium states and of the time course of infection within a host suggest that a limitation in the availability of precursor T-cells, as a consequence of high levels of recruitment into the activated pool, may play a significant role in the progression of infection in susceptible hosts. A brief discussion is presented of the implications of model prediction for therapeutic intervention.
Schweitzer
A N
AN
Wellcome Centre for Research on Parasitic Infections, Department of Biology, Imperial College, London, UK.
Swinton
J
J
Anderson
R M
RM
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D004198:Disease Susceptibility / Q000276:immunology; D004306:Dose-Response Relationship, Immunologic; D007113:Immunity, Innate / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007893:Leishmania donovani / Q000254:growth & development / Q000276:immunology*; D007898:Leishmaniasis, Visceral / Q000188:drug therapy / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008233:Lymphotoxin-alpha / Q000096:biosynthesis; D051379:Mice; D008954:Models, Biological; D013997:Time Factors
D007376:Interleukin-2; D008233:Lymphotoxin-alpha; D007371:Interferon-gamma