A<i>Leishmania</i>Ortholog of Macrophage Migration Inhibitory Factor Modulates Host Macrophage Responses

Kamir, Daniela; Zierow, Swen; Leng, Lin; Cho, Yoon Sang; Díaz, Yira Rosalba; Griffith, Jason W.; McDonald, Courtney; Merk, Melanie; Mitchell, Robert A.; Trent, John O.; Chen, Yibang; Kwong, Yuen-Kwan Amy; Xiong, Huabao; Vermeire, Jon J.; Cappello, Michael; McMahon-Pratt, Diane; Walker, Susan; Bernhagen, Jürgen; Lolis, Elias; Bucala, Richard

doi:10.4049/jimmunol.180.12.8250

Cited by 95 publications

(134 citation statements)

References 56 publications

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“…Notably, parasite MIF orthologs have been identified in several evolutionarily distant species of helminthic and protozoan pathogens (29). The close structural similarities between these parasite orthologs and mammalian MIF, together with evidence that these orthologs bind the MIF receptor (58,59), suggest that parasite proteins also may act to modulate the adaptive immune responses of their hosts.…”

Section: Discussionmentioning

confidence: 99%

APlasmodium-encoded cytokine suppresses T-cell immunity during malaria

Sun¹,

Holowka²,

Song³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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116

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The inability to acquire protective immunity against Plasmodia is the chief obstacle to malaria control, and inadequate T-cell responses may facilitate persistent blood-stage infection. Malaria is characterized by a highly inflammatory cytokine milieu, and the lack of effective protection against infection suggests that memory T cells are not adequately formed or maintained. Using a genetically targeted strain of Plasmodium berghei, we observed that the Plasmodium ortholog of macrophage migration inhibitory factor enhanced inflammatory cytokine production and also induced antigen-experienced CD4 T cells to develop into short-lived effector cells rather than memory precursor cells. The short-lived effector CD4 T cells were more susceptible to Bcl-2–associated apoptosis, resulting in decreased CD4 T-cell recall responses against challenge infections. These findings indicate that Plasmodia actively interfere with the development of immunological memory and may account for the evolutionary conservation of parasite macrophage migration inhibitory factor orthologs.

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Section: Discussionmentioning

confidence: 99%

APlasmodium-encoded cytokine suppresses T-cell immunity during malaria

Sun¹,

Holowka²,

Song³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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116

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“…The T. vaginalis genome (www.trichdb.org) encodes a single MIF homolog (Tvag_219770). This protein, TvMIF, has 31% identity to HuMIF and contains all nine invariant residues (33) found in other eukaryotic MIFs (marked in red in Fig. 1A).…”

Section: Resultsmentioning

confidence: 99%

“…Recent studies have shown that several parasitic eukaryotes encode MIF-like proteins with considerable structural and biological similarity to their mammalian hosts (31)(32)(33)(34). These parasite MIF proteins have been shown to modulate host immune Significance Prostate cancer is the most common nonskin cancer in America and the fifth most common cancer worldwide.…”

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confidence: 99%

Trichomonas vaginalis homolog of macrophage migration inhibitory factor induces prostate cell growth, invasiveness, and inflammatory responses

Twu¹,

Dessì

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

149

138

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Significance Prostate cancer is the most common nonskin cancer in America and the fifth most common cancer worldwide. Inflammation is implicated in the initiation and progression of prostate cancer; however, sources of inflammation remain unidentified. Trichomonas vaginalis is a prevalent parasite that infects prostate epithelium and is associated with an increase in aggressive prostate cancer. Here, we demonstrate that a secreted T. vaginalis protein homologous to human macrophage migration inhibitory factor elicits antibodies in infected individuals, increases prostate cell proliferation and invasiveness, and induces cellular pathways linked to inflammation. This study demonstrates that a specific parasite-derived protein can mimic its human homolog to increase inflammation and cell proliferation, which, in turn, may result in the promotion and progression of prostate cancer.

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“…The existence of two genes that exhibit signifi cant sequence identity with mammalian MIF in the genome of Leishmania genus suggests a physiological role for macrophage migration inhibitory factor-like protein (MIF1 and MIF2) in the parasite life cycle and the establishment of these orthologues as virulence factors [24][25][26] . To date, the biological activities described for the L. major MIF orthologues include the induction of macrophage migration and an anti-apoptotic activity that could be responsible for the intracellular persistence of Leishmania in macrophages; thus, these MIF orthologues may be related to the clinical outcome 25 .…”

Section: Introductionmentioning

confidence: 99%

“…Two genes that encode orthologues of human macrophage migration inhibitory factor (MIF) in the Leishmania genus have been described [24][25][26] . Human MIF is a major mediator of infl ammation.…”

Section: Introductionmentioning

confidence: 99%

Genes that encodes NAGT, MIF1 and MIF2 are not virulence factors for kala-azar caused by Leishmania infantum

Aguiar

Coelho

Costa

et al. 2014

Rev. Soc. Bras. Med. Trop.

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Introduction: Kala-azar is a disease resulting from infection by Leishmania donovani and Leishmania infantum. Most patients with the disease exhibit prolonged fever, wasting, anemia and hepatosplenomegaly without complications. However, some patients develop severe disease with hemorrhagic manifestations, bacterial infections, jaundice, and edema dyspnea, among other symptoms, followed by death. Among the parasite molecules that might infl uence the disease severity are the macrophage migration inhibitory factor-like proteins (MIF1 and MIF2) and N-acetylglucosamine-1-phosphotransferase (NAGT), which act in the fi rst step of protein N-glycosylation. This study aimed to determine whether MIF1, MIF2 and NAGT are virulence factors for severe kala-azar. Methods: To determine the parasite genotype in kala-azar patients from Northeastern Brazil, we sequenced the NAGT genes of L. infantum from 68 patients as well as the MIF1 and MIF2 genes from 76 different subjects with diverse clinical manifestations. After polymerase chain reaction (PCR), the fragments were sequenced, followed by polymorphism identifi cation. Results: The nucleotide sequencing of the 144 amplicons revealed the absence of genetic variability of the NAGT, MIF1 and MIF2 genes between the isolates. The conservation of these genes suggests that the clinical variability of kala-azar does not depend upon these genes. Additionally, this conservation suggests that these genes may be critical for parasite survival. Conclusions: NAGT, MIF1 and MIF2 do not alter the severity of kala-azar. NAGT, MIF1 and MIF2 are highly conserved among different isolates of identical species and exhibit potential for use in phylogenetic inferences or molecular diagnosis.

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ALeishmaniaOrtholog of Macrophage Migration Inhibitory Factor Modulates Host Macrophage Responses

Cited by 95 publications

References 56 publications

APlasmodium-encoded cytokine suppresses T-cell immunity during malaria

APlasmodium-encoded cytokine suppresses T-cell immunity during malaria

Trichomonas vaginalis homolog of macrophage migration inhibitory factor induces prostate cell growth, invasiveness, and inflammatory responses

Genes that encodes NAGT, MIF1 and MIF2 are not virulence factors for kala-azar caused by Leishmania infantum

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