<italic toggle="yes">Trichomonas vaginalis</italic> 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...

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Autores principales:	Yi-Pei Chen, Olivia Twu, Patricia J. Johnson
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	Trichomonas vaginalis apoptosis macrophage migration inhibitory factor nutrient starvation Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/c89c1be8beb14db08ebd0b48c5cc9291
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spelling	oai:doaj.org-article:c89c1be8beb14db08ebd0b48c5cc92912021-11-15T16:00:25Z<italic toggle="yes">Trichomonas vaginalis</italic> Macrophage Migration Inhibitory Factor Mediates Parasite Survival during Nutrient Stress10.1128/mBio.00910-182150-7511https://doaj.org/article/c89c1be8beb14db08ebd0b48c5cc92912018-07-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00910-18https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE Macrophage migration inhibitory factor (MIF) is a conserved protein found in most eukaryotes which has been well characterized in mammals but poorly studied in other eukaryotes. The limited analyses of MIF proteins found in unicellular eukaryotes have focused exclusively on the effect of parasitic MIF on the mammalian host. This was the first study to assess the function of a parasite MIF in parasite biology. We demonstrate that the Trichomonas vaginalis MIF functions to suppress cell death induced by apoptosis, thereby enhancing parasite survival under adverse conditions. Our research reveals a conserved survival mechanism, shared by a parasite and its host, and indicates a role for a conserved protein in mediating cross talk in host-pathogen interactions.Yi-Pei ChenOlivia TwuPatricia J. JohnsonAmerican Society for MicrobiologyarticleTrichomonas vaginalisapoptosismacrophage migration inhibitory factornutrient starvationMicrobiologyQR1-502ENmBio, Vol 9, Iss 3 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Trichomonas vaginalis apoptosis macrophage migration inhibitory factor nutrient starvation Microbiology QR1-502
spellingShingle	Trichomonas vaginalis apoptosis macrophage migration inhibitory factor nutrient starvation Microbiology QR1-502 Yi-Pei Chen Olivia Twu Patricia J. Johnson <italic toggle="yes">Trichomonas vaginalis</italic> Macrophage Migration Inhibitory Factor Mediates Parasite Survival during Nutrient Stress
description	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. IMPORTANCE Macrophage migration inhibitory factor (MIF) is a conserved protein found in most eukaryotes which has been well characterized in mammals but poorly studied in other eukaryotes. The limited analyses of MIF proteins found in unicellular eukaryotes have focused exclusively on the effect of parasitic MIF on the mammalian host. This was the first study to assess the function of a parasite MIF in parasite biology. We demonstrate that the Trichomonas vaginalis MIF functions to suppress cell death induced by apoptosis, thereby enhancing parasite survival under adverse conditions. Our research reveals a conserved survival mechanism, shared by a parasite and its host, and indicates a role for a conserved protein in mediating cross talk in host-pathogen interactions.
format	article
author	Yi-Pei Chen Olivia Twu Patricia J. Johnson
author_facet	Yi-Pei Chen Olivia Twu Patricia J. Johnson
author_sort	Yi-Pei Chen
title	<italic toggle="yes">Trichomonas vaginalis</italic> Macrophage Migration Inhibitory Factor Mediates Parasite Survival during Nutrient Stress
title_short	<italic toggle="yes">Trichomonas vaginalis</italic> Macrophage Migration Inhibitory Factor Mediates Parasite Survival during Nutrient Stress
title_full	<italic toggle="yes">Trichomonas vaginalis</italic> Macrophage Migration Inhibitory Factor Mediates Parasite Survival during Nutrient Stress
title_fullStr	<italic toggle="yes">Trichomonas vaginalis</italic> Macrophage Migration Inhibitory Factor Mediates Parasite Survival during Nutrient Stress
title_full_unstemmed	<italic toggle="yes">Trichomonas vaginalis</italic> Macrophage Migration Inhibitory Factor Mediates Parasite Survival during Nutrient Stress
title_sort	<italic toggle="yes">trichomonas vaginalis</italic> macrophage migration inhibitory factor mediates parasite survival during nutrient stress
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/c89c1be8beb14db08ebd0b48c5cc9291
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<italic toggle="yes">Trichomonas vaginalis</italic> Macrophage Migration Inhibitory Factor Mediates Parasite Survival during Nutrient Stress

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