Brugia malayi miRNAs and potential targets within the feline host (Felis catus)

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Host specificity is a critical feature of the survival and proliferation of parasites. In the context of interactions with the host, numerous mechanisms have been identified, particularly in parasitic helminths, that enable manipulation of the host immune system to enhance their own survival. The evolutionary history of these interactions often results in hosts becoming disease-tolerant or asymptomatic, even when burdened with a high number of worms, until a disruption in the host’s immune system can trigger a disease state. However, the molecular mechanisms underlying host specificity and the ways in which parasites alter the host’s immune system remain largely unexplored. Research conducted on parasite-derived microRNAs (miRNAs) suggests they may play a role in remodeling the host to improve parasite survival and growth, possibly through directed pathology. To further explore this host-parasite relationship, we analyzed plasma of four cats experimentally infected with the filarial nematode Brugia malayi , each with varying levels of microfilaremia, six months post-infection. Out of approximately 32 million sequencing reads, we detected 185 mature miRNA candidates potentially originating from B. malayi , with 26 miRNAs present in 10 or more copies. We also identified seven immunity-related host genes (Ptgs1, Irf4, Irf5, Numbl, Tnfsf15, Stat3, and Txlnb) that are predicted to be targets of parasite-derived miRNAs. Additional investigation is warranted to elucidate the role of these miRNAs in the host-parasite interaction. These data offer promising targets for further exploration, and potentially the discovery of novel therapeutics that disrupt parasite immune evasion and pathological alterations to the host. • The first analysis of Brugia malayi miRNA-host interactions was conducted in a feline infection model. • 185 B. malayi miRNAs were detected in infected feline host plasma samples. • 26 parasite-derived miRNAs were identified with ≥ 10 sequencing reads. • Seven immune genes (Ptgs1, Irf4, Irf5, Numbl, Tnfsf15, Stat3, and Txlnb) targeted by parasite miRNAs. • MicroRNAs linked to Rap1, AGE-RAGE, and mTOR signaling pathways in host cells.

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