Characterization of the microtranscriptoma of macrophages in response to virulent, attenuated and saprophytic strains of Leptospira spp

Abstract

Leptospirosis is the zoonosis of highest incidence in the world, occurring in an endemic and epidemic manner in developing countries, of tropical and subtropical climate. Cell response to microbial agents involves important changes in gene expression and protein content of these cells, and depends on a balance between the activation of immune response for effective defense against the pathogen and tissue/cell preservation. MicroRNAs (miRNAs) are a class of small non-coding RNAs (20-22 nucleotides), with the important epigenetic role of post-transcriptional control, repressing the translation of messenger RNA. Numerous biological processes are controlled by miRNAs, such as development and cellular differentiation of organisms, growth, apoptosis, regulation of immune response, among other physiological processes, in addition to pathological processes such as cancer and degenerative diseases. MiRNAs actively regulate the immune system by participating in the formation, recruitment and function of cells of the innate and adaptive immune system. Current research indicates that many viral, parasitic and bacterial pathogens affect expression of miRNAs in host cells. However, the regulation of this important class of non-coding RNAs has not yet been investigated after infection by Leptospira. The description transcriptional and microtranscriptional changes of the host cells in response to this infection, opens up new possibilities for prognostics, diagnostic and treatment as, for example, the development of elements that stimulate or inhibit non-coding RNAs to promote efficient elimination of the pathogen. In this study, we will apply the technique of microarray associated with bioinformatic tools to identify the role of miRNAs in the response of murine macrophages to Leptospira interrogans, as well as on the differences in cellular response to infection with saprophytic and attenuated species of Leptospira. (AU)