Circulating inflammatory mediators as biomarkers of ocular toxoplasmosis in acute and in chronic infection.


Journal

Journal of leukocyte biology
ISSN: 1938-3673
Titre abrégé: J Leukoc Biol
Pays: England
ID NLM: 8405628

Informations de publication

Date de publication:
10 2020
Historique:
received: 05 01 2020
revised: 06 04 2020
accepted: 27 04 2020
pubmed: 19 5 2020
medline: 10 2 2021
entrez: 19 5 2020
Statut: ppublish

Résumé

Toxoplasmosis is highly endemic worldwide. In Brazil, depending on the geographical region and socioeconomic status, 40-70% of individuals become seropositive at some point in their lives. A significant proportion of Toxoplasma gondii-chronically infected individuals who are otherwise immunocompetent develop recurrent ocular lesions. The inflammatory/immune mechanisms involved in development of ocular lesion are still unknown and, despite previous investigation, there are no reliable immune biomarkers to predict/follow disease outcome. To better understand the impact of the immune response on parasite control and immunopathology of ocular toxoplasmosis, and to provide insights on putative biomarkers for disease monitoring, we assessed the production of a large panel of circulating immune mediators in a longitudinal study of patients with postnatally acquired toxoplasmosis stratified by the presence of ocular involvement, both at the early acute stage and 6 months later during chronic infection, correlating them with presence of ocular involvement. We found that T. gondii-infected patients, especially during the acute stage of the disease, display high levels of chemokines, cytokines, and growth factors involved in the activation, proliferation, and migration of inflammatory cells to injured tissues. In particular, major increases were found in the IFN-induced chemokines CXCL9 and CXCL10 in T. gondii-infected patients regardless of disease stage or clinical manifestations. Moreover, a specific subgroup of circulating cytokines and chemokines including GM-CSF, CCL25, CCL11, CXCL12, CXCL13, and CCL2 was identified as potential biomarkers that accurately distinguish different stages of infection and predict the occurrence of ocular toxoplasmosis. In addition to serving as predictors of disease development, these host inflammatory molecules may offer promise as candidate targets for therapeutic intervention.

Identifiants

pubmed: 32421913
doi: 10.1002/JLB.4MA0420-702R
doi:

Substances chimiques

Cytokines 0
Inflammation Mediators 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1253-1264

Informations de copyright

©2020 Society for Leukocyte Biology.

Références

Dubey JP, Jones JL. Toxoplasma gondii infection in humans and animals in the United States. Int J Parasitol. 2008;38:1257-1278.
Tenter AM, Heckeroth AR, Weiss LM. Toxoplasma gondii: from animals to humans. Int J Parasitol. 2000;30:1217-1258.
Wilking H, Thamm M, Stark K, Aebischer T, Seeber F. Prevalence, incidence estimations, and risk factors of Toxoplasma gondii infection in Germany: a representative, cross-sectional, serological study. Sci Rep. 2016;6:22551.
Pleyer U, Schluter D, Manz M. Ocular toxoplasmosis: recent aspects of pathophysiology and clinical implications. Ophthalmic Res. 2014;52:116-123.
Martins LM, Rangel AL, Peixe RG, et al. Specific IgM, IgG and IgG1 directed against Toxoplasma gondii detected by flow cytometry and their potential as serologic tools to support clinical indirect fundoscopic presumed diagnosis of ocular disease. J Immunol Methods. 2015;417:97-106.
Matowicka-Karna J, Dymicka-Piekarska V, Kemona H. Does Toxoplasma gondii infection affect the levels of IgE and cytokines (IL-5, IL-6, IL-10, IL-12, and TNF-alpha). Clin Dev Immunol. 2009;2009:374696.
Sibley LD, Howe DK. Genetic basis of pathogenicity in toxoplasmosis. Curr Top Microbiol Immunol. 1996;219:3-15.
Wong SY, Remington JS. Toxoplasmosis in pregnancy. Clin Infect Dis. 1994;18:853-861. quiz 862.
Grigg ME, Ganatra J, Boothroyd JC, Margolis TP. Unusual abundance of atypical strains associated with human ocular toxoplasmosis. J Infect Dis. 2001;184:633-639.
Gazzinelli RT, Hakim FT, Hieny S, Shearer GM, Sher A. Synergistic role of CD4+ and CD8+ T lymphocytes in IFN-gamma production and protective immunity induced by an attenuated Toxoplasma gondii vaccine. J Immunol. 1991;146:286-292.
Oliveira MA, Santiago HC, Lisboa CR, et al. Leishmania sp: comparative study with Toxoplasma gondii and Trypanosoma cruzi in their ability to initialize IL-12 and IFN-gamma synthesis. Exp Parasitol. 2000;95:96-105.
Tait ED, Hunter CA. Advances in understanding immunity to Toxoplasma gondii. Mem Inst Oswaldo Cruz. 2009;104:201-210.
Goldszmid RS, Caspar P, Rivollier A, et al. NK cell-derived interferon-gamma orchestrates cellular dynamics and the differentiation of monocytes into dendritic cells at the site of infection. Immunity. 2012;36:1047-1059.
Gazzinelli RT, Wysocka M, Hayashi S, et al. Parasite-induced IL-12 stimulates early IFN-gamma synthesis and resistance during acute infection with Toxoplasma gondii. J Immunol. 1994;153:2533-2543.
Luster AD, Ravetch J V. Biochemical characterization of a gamma interferon-inducible cytokine (IP-10). J Exp Med. 1987;166:1084-1097.
Khan IA, MacLean JA, Lee FS, et al. IP-10 is critical for effector T cell trafficking and host survival in Toxoplasma gondii infection. Immunity. 2000;12:483-494.
Gazzinelli RT, Denkers EY. Protozoan encounters with Toll-like receptor signalling pathways: implications for host parasitism. Nat Rev Immunol. 2006;6:895-906.
Yap GS, Sher A. Effector cells of both nonhemopoietic and hemopoietic origin are required for interferon (IFN)-gamma- and tumor necrosis factor (TNF)-alpha-dependent host resistance to the intracellular pathogen, Toxoplasma gondii. J Exp Med. 1999;189:1083-1092.
Gaddi PJ, Yap GS. Cytokine regulation of immunopathology in toxoplasmosis. Immunol cell Biol. 2007;85:155-159.
Vossenkämper A, Struck D, Alvarado-Esquivel C, et al. Both IL-12 and IL-18 contribute to small intestinal Th1-type immunopathology following oral infection with Toxoplasma gondii, but IL-12 is dominant over IL-18 in parasite control. Eur J Immunol. 2004;34:3197-3207.
Suzuki Y, Sher A, Yap G, et al. IL-10 is required for prevention of necrosis in the small intestine and mortality in both genetically resistant BALB/c and susceptible C57BL/6 mice following peroral infection with Toxoplasma gondii. J Immunol. 2000;164:5375-5382.
Gazzinelli RT, Wysocka M, Hieny S, et al. In the absence of endogenous IL-10, mice acutely infected with Toxoplasma gondii succumb to a lethal immune response dependent on CD4+ T cells and accompanied by overproduction of IL-12, IFN-gamma and TNF-alpha. J Immunol. 1996;157:798-805.
Malta JMAS, Cabral CM, da Nóbrega AA, et al. Surto de toxoplasmose no município de Gouveia, Minas Gerais. J Heal Biol Sci. 2019;7:233.
Luiza-Silva M, Campi-Azevedo AC, Batista MA, et al. Cytokine signatures of innate and adaptive immunity in 17DD yellow fever vaccinated children and its association with the level of neutralizing antibody. J Infect Dis. 2011;204:873-883.
Suzuki Y, Orellana MA, Schreiber RD, Remington JS. Interferon-gamma: the major mediator of resistance against Toxoplasma gondii. Science (80-). 1988;240:516-518.
Mordue DG, Monroy F, La Regina M, Dinarello CA, Sibley LD. Acute toxoplasmosis leads to lethal overproduction of Th1 cytokines. J Immunol. 2001;167:4574-4584.
de Araújo TE, Coelho-Dos-Reis JG, Béla SR, et al. Early serum biomarker networks in infants with distinct retinochoroidal lesion status of congenital toxoplasmosis. Cytokine. 2017;95:102-112.
Andrade WA, Souza Mdo C, Ramos-Martinez E, et al. Combined action of nucleic acid-sensing Toll-like receptors and TLR11/TLR12 heterodimers imparts resistance to Toxoplasma gondii in mice. Cell Host Microbe. 2013;13:42-53.
Dunay IR, Damatta RA, Fux B, et al. Gr1(+) inflammatory monocytes are required for mucosal resistance to the pathogen Toxoplasma gondii. Immunity. 2008;29:306-317.
Tosh KW, Mittereder L, Bonne-Annee S, et al. The IL-12 Response of primary human dendritic cells and monocytes to Toxoplasma gondii is stimulated by phagocytosis of live parasites rather than host cell invasion. J Immunol. 2016;196:345-356.
Dufour JH, Dziejman M, Liu MT, Leung JH, Lane TE, Luster AD. IFN-gamma-inducible protein 10 (IP-10; CXCL10)-deficient mice reveal a role for IP-10 in effector T cell generation and trafficking. J Immunol. 2002;168:3195-3204.
Norose K, Kikumura A, Luster AD, Hunter CA, Harris TH. CXCL10 is required to maintain T-cell populations and to control parasite replication during chronic ocular toxoplasmosis. Investig Ophthalmol Vis Sci. 2011;52:389-398.
Kumar A, Humphreys TD, Kremer KN, et al. CXCR4 physically associates with the T cell receptor to signal in T cells. Immunity. 2006;25:213-224.
Legler DF, Loetscher M, Roos RS, Clark-Lewis I, Baggiolini M, Moser B. B cell-attracting chemokine 1, a human CXC chemokine expressed in lymphoid tissues, selectively attracts B lymphocytes via BLR1/CXCR5. J Exp Med. 1998;187:655-660.
Ansel KM, McHeyzer-Williams LJ, Ngo VN, McHeyzer-Williams MG, Cyster JG. In vivo-activated CD4 T cells upregulate CXC chemokine receptor 5 and reprogram their response to lymphoid chemokines. J Exp Med. 1999;190:1123-1134.
Reiss Y, Proudfoot AE, Power CA, Campbell JJ, Butcher EC. CC chemokine receptor (CCR)4 and the CCR10 ligand cutaneous T cell-attracting chemokine (CTACK) in lymphocyte trafficking to inflamed skin. J Exp Med. 2001;194:1541-1547.
Aviles H, Stiles J, O'Donnell P, et al. Kinetics of systemic cytokine and brain chemokine gene expression in murine toxoplasma infection. J Parasitol. 2008;94:1282-1288.
Ledee DR, Chen J, Tonelli LH, Takase H, Gery I, Zelenka PS. Differential expression of splice variants of chemokine CCL27 mRNA in lens, cornea, and retina of the normal mouse eye. Mol Vis. 2004;10:663-667.
Furusato E, Shen D, Cao X, et al. Inflammatory cytokine and chemokine expression in sympathetic ophthalmia: a pilot study. Histol Histopathol. 2011;26:1145-1151.
Kitaichi N, Kotake S, Sasamoto Y, et al. Prominent increase of macrophage migration inhibitory factor in the sera of patients with uveitis. Invest Ophthalmol Vis Sci. 1999;40:247-250.
Taguchi C, Sugita S, Tagawa Y, Nishihira J, Mochizuki M. Macrophage migration inhibitory factor in ocular fluids of patients with uveitis. Br J Ophthalmol. 2001;85:1367-1371.

Auteurs

Ana Pmp Marino (AP)

Laboratório de Biologia e Imunologia de Doenças Infecciosas e Parasitárias, Instituto René Rachou, Fundação Oswaldo Cruz-Fiocruz, Belo Horizonte, Minas Gerais, Brazil.

Luara I Dos Santos (LI)

Laboratório de Biologia e Imunologia de Doenças Infecciosas e Parasitárias, Instituto René Rachou, Fundação Oswaldo Cruz-Fiocruz, Belo Horizonte, Minas Gerais, Brazil.
Faculdade de Ciências Médicas de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

Priscilla M Henriques (PM)

Laboratório de Biologia e Imunologia de Doenças Infecciosas e Parasitárias, Instituto René Rachou, Fundação Oswaldo Cruz-Fiocruz, Belo Horizonte, Minas Gerais, Brazil.

Ester Roffe (E)

Laboratório de Biologia e Imunologia de Doenças Infecciosas e Parasitárias, Instituto René Rachou, Fundação Oswaldo Cruz-Fiocruz, Belo Horizonte, Minas Gerais, Brazil.
Laboratory of Molecular Immunology, Molecular Signaling Section, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

Daniel V Vasconcelos-Santos (DV)

Department of Ophthalmology and Otorinolaryngology, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

Alan Sher (A)

Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

Dragana Jankovic (D)

Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.

Matheus S Gomes (MS)

Rede Multidisciplinar de Pesquisa, Ciência e Tecnologia, Universidade Federal de Uberlândia, Patos de Minas, Minas Gerais, Brasil.
Laboratório de Bioinformática e Análises Moleculares, Universidade Federal de Uberlândia, Patos de Minas, Minas Gerais, Brasil.

Laurence R Amaral (LR)

Rede Multidisciplinar de Pesquisa, Ciência e Tecnologia, Universidade Federal de Uberlândia, Patos de Minas, Minas Gerais, Brasil.
Laboratório de Bioinformática e Análises Moleculares, Universidade Federal de Uberlândia, Patos de Minas, Minas Gerais, Brasil.

Ana C Campi-Azevedo (AC)

Grupo Integrado de Pesquisas em Biomarcadores, Instituto René Rachou, Fundação Oswaldo Cruz-Fiocruz, Belo Horizonte, Minas Gerais, Brazil.

Andréa Teixeira-Carvalho (A)

Grupo Integrado de Pesquisas em Biomarcadores, Instituto René Rachou, Fundação Oswaldo Cruz-Fiocruz, Belo Horizonte, Minas Gerais, Brazil.

Olindo A Martins-Filho (OA)

Grupo Integrado de Pesquisas em Biomarcadores, Instituto René Rachou, Fundação Oswaldo Cruz-Fiocruz, Belo Horizonte, Minas Gerais, Brazil.

Ricardo T Gazzinelli (RT)

Laboratório de Imunopatologia, Instituto René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil.

Lis R Antonelli (LR)

Laboratório de Biologia e Imunologia de Doenças Infecciosas e Parasitárias, Instituto René Rachou, Fundação Oswaldo Cruz-Fiocruz, Belo Horizonte, Minas Gerais, Brazil.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH