Is there a direct role for erythrocytes in the immune response?

Erythrocytes are highly abundant circulating cells in the vertebrates, which, with the notable exception of mammals, remain nucleated throughout the entire life cycle. The major function associated with these cells is respiratory gas exchange however other functions including interaction with the immune system have been attributed to these cells. Many viral, prokaryotic and eukaryotic pathogens directly target this cell type and across the vertebrate group a significant number of related pathologies have been reported. Across the primary literature mechanisms of interaction, invasion and replication between viruses and erythrocytes have been well described however the functional response of the erythrocyte has been poorly studied. A fragmented series of reports spanning the vertebrates suggests that these cells are capable of functional responses to viral infection. In contrast, in-depth proteomic studies using human erythrocytes have strongly progressed throughout the past decade providing a rich source of information related to protein expression and potential function. Furthermore information at the gene expression level is becoming available. Here we provide a review of erythrocyte-pathogen interactions, erythrocyte functions in immunity and propose in light of recent -omics research that the nucleated erythrocytes may have a direct role in the immune response.