Abstract
Visceral leishmaniasis is characterized by mixed production of Th1/2 cytokines and the disease is established by an enhanced level of Th2 cytokine. CD4+ T cells are main cell type which produces Th1/2 cytokine in the host upon Leishmania infection. However, the regulatory mechanism for Th1/2 production is not well understood. In this study, we co-cultured mice CD4+ T cells with Leishmania donovani infected and uninfected macrophage for the identification of dysregulated miRNAs in CD4+ T cells by next-generation sequencing. Here, we identified 604 and 613 known miRNAs in CD4+ T cells in control and infected samples respectively and a total of only 503 miRNAs were common in both groups. The expression analysis revealed that 112 miRNAs were up and 96 were down-regulated in infected groups, compared to uninfected control. Nineteen up-regulated and 17 down-regulated miRNAs were statistically significant (p < 0.05), which were validated by qPCR. Further, using insilco approach, we identified the gene targets of significant miRNAs on the basis of CD4+ T cell biology. Eleven up-regulated miRNAs and 9 down-regulated miRNAs were associated with the cellular immune responses and Th1/2 dichotomy upon Leishmania donovani infection. The up-regulated miRNAs targeted transcription factors that promote differentiation of CD4+ T cells towards Th1 phenotype. While down-regulated miRNAs targeted the transcription factors that facilitate differentiation of CD4+ T cells towards Th2 populations. The GO and pathway enrichment analysis also showed that the identified miRNAs target the pathway and genes related to CD4+ T cell biology which plays important role in Leishmania donovani infection.
Highlights
Visceral leishmaniasis is characterized by mixed production of Th1/2 cytokines and the disease is established by an enhanced level of Th2 cytokine
Leishmaniasis has been included among thirteen neglected tropical parasitic diseases by world health organization (WHO), which is caused by intracellular protozoan parasites of the genus Leishmania
After Leishmania infection, naive CD4+ T cells differentiate into specific T cells type such as T regulatory (Treg), Th17, Th1 and Th2 depending upon immune response and expression of specific transcription factors[6]
Summary
Visceral leishmaniasis is characterized by mixed production of Th1/2 cytokines and the disease is established by an enhanced level of Th2 cytokine. The GO and pathway enrichment analysis showed that the identified miRNAs target the pathway and genes related to CD4+ T cell biology which plays important role in Leishmania donovani infection. Among T cells, the CD4+ T cells are known to play a central role in regulating cellular immune responses during Leishmania donovani infection[5]. After Leishmania infection, naive CD4+ T cells differentiate into specific T cells type such as T regulatory (Treg), Th17, Th1 and Th2 depending upon immune response and expression of specific transcription factors[6]. MicroRNAs (miRNAs) are single-stranded molecules having length of 19 to 25 nucleotides They have been found to play a significant role in various human disease pathogeneses[11]. A single miRNA can target more than hundred to thousand genes and are know to regulate DNA transcription, methylation, and histone acetylation as well[14]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
