Changed immune and miRNA response in RAW264.7 cells infected with cell wall deficient mycobacterium tuberculosis

Abstract

Cell wall deficient (CWD) forms of Mycobacterium tuberculosis (Mtb) confers a marked resistance to immune system of the host. However, there is limit data on the effect of intracellular CWD-Mtb infection on macrophages. In the study, effects of CWD-Mtb on cell viability, cytokine response and miRNA expression of macrophages were analyzed. Cell viability was reduced, levels of interleukin-1α (IL-1α), IL-1β, IL-6, IL-10 and interferon-γ (IFN-γ) were also significantly changed after infection of RAW264.7 cells with CWD-Mtb. A total of 105 miRNAs were deregulated between CWD-Mtb and wild Mtb group, and among them, miR-29b was upregulated in CWD-Mtb group. Downregulation of miR-29b resulted in significant elevation level of IFN-γ mRNA. Involved signaling pathways of potential target genes of differentially expressed miRNAs mainly focused on T cell receptor signaling pathway, MAPK signaling pathway, neurotrophin signaling pathway, and regulation of actin cytoskeleton. Taken together, the results showed that cytokine production of CWD-Mtb infected macrophages was altered and many miRNAs were involved in regulation of macrophage response to CWD-Mtb infection, which probably determined the differential outcome following different phenotype Mtb infection. These findings open up a new and interesting avenue for an improved understanding of pathogenesis of CWD-Mtb.