27 August 2002

by Martin F. Bachmann bachmann@cytos.com
 

Adaptive immunity is essential for protection against viral infections. Dependent on the type of virus, protection from primary infection can be mediated by antibodies and/or T cells, whereas protection from secondary infection is usually largely dependent on antibodies. Components of the innate immune system are known to be important to increase anti-viral protection, a good example being complement, as complement degradation products enhance targeting of viral antigens to lymphoid organs and increase both anti-viral B and T cell responses. Thus, at least for the complement system, innate immunity primarily acts on anti-viral protection by enhancing adaptive immunity.

The study by Oehen et al. now clearly shows that marginal zone and sinusoidal macrophages, specialized cell populations in the spleen and lymph nodes, respectively, are key for protection against lethal infection with vesicular stomatitis virus (VSV) or lymphocytic choriomeningitis virus (LCMV). Surprisingly, the protective function of the macrophages did not correlate with enhanced adaptive immunity. Specifically, mice deficient for marginal zone and sinusoidal macrophages mounted normal antibody and cytotoxic T cell responses against VSV and LCMV, respectively. Yet they could not control the virus and died upon infection. Interestingly, the macrophages were essential for early containment of the infection, at time points before adaptive immunity kicks in. Thus, rather than enhancing specific anti-viral B and T cell responses, the macrophage populations appeared to be directly involved in anti-viral protection.

How this may happen? Both LCMV and VSV are efficiently filtered out from the circulation by marginal zone macrophages, probably via recognition mediated by scavenger or complement receptors and alike. The ingested particles are expected to induce a defense program in the macrophage population, in part by activation of toll like receptor 3. Upon activation of macrophages, viral particles may be digested in lysozomes rather than undergoing productive replication cycles. Thus, viral load is reduced early after infection, numerically facilitating the adaptive immune system`s task to rid the infection. Much remains to be investigated on the biology of macrophages. After research on dendritic cells has revolutionized immunology, it might now be time to have a closer look at the properties and in vivo functions of macrophages.