Porcine Respiratory and Reproductive Syndrome Virus (PRRSV) infection is a major concern for swine industry. Our partial understanding of the interactions between the virus and the immune system is the major reason for the lack of efficient control measures. The PRRS virus replicates mainly in the pulmonary macrophages which: (1) are responsible for inflammation and viral destruction by phagocytosis; and (2) participate in the induction and orientation of the adaptive immune response. Consequently, macrophage infection hampers the whole immune response. The interactions between macrophages and virus during the first steps of infection have not been thoroughly investigated and their influence on the infection resolution is unknown. Here, we propose an original model simulating immune and infection dynamics to explore these complex mechanisms and test biological hypotheses. We highly detail the immune functions and infectious statuses of macrophages and take into account interactions between innate and adaptive responses and cytokines regulations. We use the model to study the relative influence of macrophage – virus interactions on the infection resolution comparatively to adaptive mechanisms.