Trichomonas vaginalis Macrophage Migration Inhibitory Factor Mediates Parasite Survival during Nutrient Stress

Abstract

Trichomonas vaginalis is responsible for the most prevalent non-viral sexually transmitted disease worldwide, and yet the mechanisms used by this parasite to establish and maintain infection are poorly understood. We previously identified a T. vaginalis homologue (TvMIF) of a human cytokine, human macrophage migration inhibitory factor (huMIF). TvMIF mimics huMIF’s role in increasing cell growth and inhibiting apoptosis in human host cells. To interrogate a role of TvMIF in parasite survival during infection, we asked whether overexpression of TvMIF (TvMIF-OE) confers an advantage to the parasite under nutrient stress conditions by comparing the survival of TvMIF-OE parasites to that of empty vector (EV) parasites. We found that under conditions of serum starvation, overexpression of TvMIF resulted in increased parasite survival. Serum-starved parasites secrete 2.5-fold more intrinsic TvMIF than unstarved parasites, stimulating autocrine and paracrine signaling. Similarly, we observed that addition of recombinant TvMIF increased the survival of the parasites in the absence of serum. Recombinant huMIF likewise increased the parasite survival in the absence of serum, indicating that the parasite may use this host survival factor to resist its own death. Moreover, TvMIF-OE parasites were found to undergo significantly less apoptosis and reactive oxygen species (ROS) generation under conditions of serum starvation, consistent with increased survival being the result of blocking ROS-induced apoptosis. These studies demonstrated that a parasitic MIF enhances survival under adverse conditions and defined TvMIF and huMIF as conserved survival factors that exhibit cross talk in host-pathogen interactions.

Macrophage Migration Inhibitory Factor in Psoroptes ovis: Molecular Characterization and Potential Role in Eosinophil Accumulation of Skin in Rabbit and Its Implication in the Host–Parasite Interaction

“…Additionally, MIF has been reported to enhance Myzus percicae and Acyrthosiphon pisum feeding [ 26 ], so we suggested that the high abundance expression of MIF in female mites might be related to this stage need for feeding a large amount of food to acquire nutrients before oviposition [ 26 ]. Additionally, MIF appeared with a higher transcript expression in starved mites, suggesting that Pso MIF may be beneficial for enhancing P. ovis survival under malnourished conditions [ 23 , 27 ] or seeking host or initiating feeding behavior [ 28 ], and that this similar function of MIF could increase parasite survival under adverse nutrient stress condition has been confirmed in Trichomonas vaginalis [ 27 ]. Several studies reported that MIF was clearly detectable in excretory/secretory products of the parasite [ 25 , 29 ], and the MIF was secreted by the parasite into host tissue and blood during infection [ 30 ].…”

Influence of Trichomonas vaginalis macrophage migration inhibitory factor on the proliferation activity of prostate epithelial cell line and its preliminary mechanism

“…The pathogenesis of trichomonas vaginalis to prostate disease is still unclear, so the treatment of such patients cannot yield the best‐expected results. As a crucial index after Trichomonas vaginalis, TvMIF can accurately restore infection status and MIF with the exact mechanism, since TvMIF has been verified to play a crucial role in the promotion of prostate disease development (Chen et al, 2018). Therefore, it is imperative that clinical research fully understands and explore the influence of TvMIF on the prostate.…”

Infinity war: Trichomonas vaginalis and interactions with host immune response

“…During nutrient deprivation, overexpressed T. vaginalis macrophage migration inhibitory factor (TvMIF) was detected, which is a human cytokine homolog that mimics the HuMIF (human macrophage migration inhibitory factor). It has been proposed that this overexpression of TvMIF can inhibit ROS production and prevent ROS-induced apoptosis [24,25]. Interestingly, reactive nitrogen intermediates (RNI) may be associated with establishing an infection.…”