Nucleated erythrocytes in the vertebrates. A new cellular paradigm in the immune response

Resumen

Erythrocytes represent the most abundant cell type of the bloodstream in all vertebrates. The principal feature that differentiates the erythrocytes of non-mammalian vertebrates from the mammals is that mammals they maintain the nucleus throughout their. While the main function associated to erythrocytes is O2 and CO2 transport, other non-respiratory functions have been attributed to these cells. In this study we hypothesized that nucleated erythrocytes of two phylogenetically distant species, rainbow trout (Oncorhynchus mykiss) and domesticated chicken (Gallus gallus), can participate in an active fashion in the immune response and likely contributing to the resolution of infectious states. Our data shows that trout and chicken erythrocytes express mRNAs for pathogen recognition receptors (PRRs). In response to pathogen associated molecular patterns (PAMPs) stimulations, erythrocytes activated transcriptional regulation of mRNAs related to the immune response that is PAMP- and time-dependent. The trout erythrocyte transcriptome was obtained by RNA-Seq revealing mRNA transcripts related to the innate and adaptive immune response including receptors, cytokines and chemokines. Furthermore, the transcriptome contains other interesting mRNAs that code for hormone receptors, growth factors and enzymes involved in eicosanoid and steroid synthesis and metabolism highlighting an integrated role of erythrocytes into the organism. Studies on post-transcriptional regulation using density gradients indicated increased polysome-bound mRNA after poly (I:C) stimulation suggesting mRNA translation and production of protein. Finally, we show that PAMP-activated erythrocytes release into the medium thermolabile molecules that modulate the antiviral response in fish and birds. In conclusion, in this thesis we demonstrate that nucleated erythrocytes of non-mammalian vertebrates have a role in the immune response and likely participate with other physiological systems.