quantitative analysis of immune response and erythropoiesis during rodent malarial infection定量分析在啮齿动物的免疫反应和红细胞生成疟疾感染.pdfVIP

Quantitative Analysis of Immune Response and Erythropoiesis during Rodent Malarial Infection 1 ˚ 2 3 1 Martin R. Miller , Lars Raberg , Andrew F. Read , Nicholas J. Savill * 1 Centre for Infectious Diseases, Institute of Immunology and Infection Research, University of Edinburgh, Edinburgh, United Kingdom, 2 Department of Animal Ecology, Lund University, Lund, Sweden, 3 Center for Infectious Disease Dynamics and Departments of Biology and Entomology, Pennsylvania State University, University Park, Pennsylvania, United States of America Abstract Malarial infection is associated with complex immune and erythropoietic responses in the host. A quantitative understanding of these processes is essential to help inform malaria therapy and for the design of effective vaccines. In this study, we use a statistical model-fitting approach to investigate the immune and erythropoietic responses in Plasmodium chabaudi infections of mice. Three mouse phenotypes (wildtype, T-cell-deficient nude mice, and nude mice reconstituted with T-cells taken from wildtype mice) were infected with one of two parasite clones (AS or AJ). Under a Bayesian framework, we use an adaptive population-based Markov chain Monte Carlo method and fit a set of dynamical models to observed data on parasite and red blood cell (RBC) densities. Model fits are compared using Bayes’ factors and parameter estimates obtained. We consider three independent immune mechanisms: clearance of parasitised RBCs (pRBC), clearance of unparasitised RBCs (uRBC), and clearance of parasites that burst from RBCs (merozoites). Our results sugges