Long Noncoding RNA Mir17hg and D43Rik Control the Macrophage Response to Toxoplasma gondii Infection

Abstract

Long noncoding (lnc) RNAs are emerging as imported regulators of immunity but how they impact the host response to infection is still largely unknown. In previous screening studies we identified Mir17hg and D43Rik as host lncRNAs upregulated in mouse bone marrow-derived macrophages regardless of parasite strain type. Here, we examined the impact of Mir17hg and D43Rik during infection of macrophages. Expression of these lncRNAs was transiently increased by T. gondii, peaking 6 hr post infection and falling to background noninfected levels by 18 hrs. Both Mir17hg and D43Rik were predominantly localized to the host cell nucleus, suggesting roles in gene regulation. Using a lncRNA silencing approach mediated by siRNA, we uncovered evidence that both D43Rik and Mir17hg were involved in modulating the host transcriptional response to infection with Type I and Type II strains of Toxoplasma. These effects were most dramatic during infection with the high virulence Type I RH, where Mir17hg silencing resulted in increased expression of a broad panel of immunity-related genes. Our results implicate lncRNAs Mir17hg and D43Rik as important molecular regulators of the macrophage response to Toxoplasma.