CRUCIAL ROLE OF MARGINAL ZONE MACROPHAGES AND MARGINAL ZONE METALLOPHILS IN THE CLEARANCE OF LYMPHOCYTIC CHORIOMENINGITIS VIRUS-INFECTION

Macrophages play a key role in the immune defense against pathogens. T hey control early invasion by antigen-unspecific phagocytosis of patho gens and act as professional antigen-presenting cells to induce antige n-specific T cell responses. To investigate the involvement of particu lar subsets of the splenic macrophages in an antiviral immune response , we selectively depleted mice of splenic marginal zone macrophages (M ZM) and marginal zone metallophils (MM) using the clodronate liposome depletion technique. MZM- and MM-depleted mice were not able to contro l an infection with lymphocytic choriomeningitis virus (LCMV). In thes e mice, LCMV spread from the spleen to peripheral organs at an early p hase of infection, The virus-specific cytotoxic T lymphocyte (CTL) res ponse was induced initially, yet was exhausted in parallel with the ov erwhelming virus replication. These findings suggest that MZM and MM p lay a crucial role in the early control of a LCMV infection by prevent ing immediate virus spread to peripheral organs, but are not essential for the induction of the LCMV-specific CTL response.