Immune Mediator Profile in Aqueous Humor Differs in Patients with Primary Acquired Ocular Toxoplasmosis and Recurrent Acute Ocular Toxoplasmosis

Overview

Journal Mediators Inflamm

Publisher Wiley

Specialties Biochemistry
Pathology

Date 2019 Mar 26

PMID 30906227

Citations 9

Authors

Claudia Thieme

Stephan Schlickeiser

Sylvia Metzner

Claudia Dames

Uwe Pleyer

Affiliations

Soon will be listed here.

Abstract

Purpose: To compare the intraocular cytokine and chemokine profiles in patients with acute primary acquired ocular toxoplasmosis (pOT) or recurrent ocular toxoplasmosis (rOT) and to correlate them with their clinical characteristics.

Methods: Aqueous humor samples were collected from 62 consecutive patients (21 pOT, 30 rOT, and 11 noninfected controls) and analyzed by multiplex assay. Correlations were assessed between cytokine/chemokine levels, type of inflammatory response (T1, T2, and T17), and clinical characteristics. In all OT patients, the clinical diagnosis of either pOT or rOT was confirmed by positive intraocular Goldmann/Witmer-Desmonts coefficient. Correlations were assessed between a preselected panel of immune mediators and the clinical characteristics of OT.

Results: In pOT patients, increased levels of IL-2, IFN-, TNF-, IL-15, IL-4, IL-5, IL-9, IL-13, IL-17, IL-1R, IL-6, IL-1, and chemokines MIP-1, MIP-1, IP-10, Eotaxin, IL-8, RANTES, PDGF-bb, GM-CSF, G-CSF, and MCP-1 were found in comparison to those in controls ( < 0.05). Patients with rOT showed elevated levels of IL-2, IFN-, TNF-, IL-15, IL-4, IL-5, IL-9, IL-17, IL-1R, IL-6, IL-1, and chemokines MIP-1, IP-10, Eotaxin, IL-8, RANTES, PDGF-bb, G-CSF, and MCP-1 compared to controls ( < 0.05). In addition, IL-7 ( = 0.028) differed between pOT and rOT; IL-9 ( = 0.054) and IL-13 ( = 0.051) showed a tendency of higher concentration in pOT than in rOT. A negative correlation was found between IL-7 ( = 0.017) as well as IL-9 ( = 0.008) and the number of recurrences. Cytokine ratios showed no difference between pOT and rOT, indicating a dominant T1-type response in both infectious groups. Moreover, a positive correlation was detected between IL-7, VEGF, IL-13 and age at aqueous humor sampling ( < 0.05).

Conclusions: This study for the first time shows subtle differences between the intraocular cytokine profiles in patients with either acute pOT or rOT.

Citing Articles

The role of age in ocular toxoplasmosis: clinical signs of immunosenescence and inflammaging.

Eraghi A, Garweg J, Pleyer U Front Med (Lausanne). 2024; 11:1311145.

PMID: 38504919 PMC: 10950095. DOI: 10.3389/fmed.2024.1311145.

Dynamic Immune Profile in French Toxoplasmosis Patients.

Denis J, Gommenginger C, Strechie T, Filisetti D, Beal L, Pfaff A J Infect Dis. 2022; 226(10):1834-1841.

PMID: 35978487 PMC: 9650498. DOI: 10.1093/infdis/jiac305.

Treatment Strategy in Human Ocular Toxoplasmosis: Why Antibiotics Have Failed.

Garweg J, Pleyer U J Clin Med. 2021; 10(5).

PMID: 33807871 PMC: 7961948. DOI: 10.3390/jcm10051090.

Murine Model of Primary Acquired Ocular Toxoplasmosis: Fluorescein Angiography and Multiplex Immune Mediator Profiles in the Aqueous Humor.

Li K, Feng X, Hikosaka K, Norose K Invest Ophthalmol Vis Sci. 2021; 62(3):9.

PMID: 33683297 PMC: 7960860. DOI: 10.1167/iovs.62.3.9.

Pathophysiology of ocular toxoplasmosis: Facts and open questions.

Greigert V, Bittich-Fahmi F, Pfaff A PLoS Negl Trop Dis. 2020; 14(12):e0008905.

PMID: 33382688 PMC: 7774838. DOI: 10.1371/journal.pntd.0008905.

References

Denney C, Eckmann L, Reed S . Chemokine secretion of human cells in response to Toxoplasma gondii infection. Infect Immun. 1999; 67(4):1547-52. PMC: 96495. DOI: 10.1128/IAI.67.4.1547-1552.1999. View

Ohta K, Yamagami S, Taylor A, Streilein J . IL-6 antagonizes TGF-beta and abolishes immune privilege in eyes with endotoxin-induced uveitis. Invest Ophthalmol Vis Sci. 2000; 41(9):2591-9. View

Dimier-Poisson I, Aline F, Mevelec M, Beauvillain C, Buzoni-Gatel D, Bout D . Protective mucosal Th2 immune response against Toxoplasma gondii by murine mesenteric lymph node dendritic cells. Infect Immun. 2003; 71(9):5254-65. PMC: 187296. DOI: 10.1128/IAI.71.9.5254-5265.2003. View

GOLDMANN H, WITMER R . [Antibodies in the aqueous humor]. Ophthalmologica. 1954; 127(4-5):323-30. DOI: 10.1159/000301976. View

Holland G . Ocular toxoplasmosis: a global reassessment. Part II: disease manifestations and management. Am J Ophthalmol. 2004; 137(1):1-17. View

Hughes H . Oxidative killing of intracellular parasites mediated by macrophages. Parasitol Today. 1988; 4(12):340-7. DOI: 10.1016/0169-4758(88)90003-8. View

Jabs D, Nussenblatt R, Rosenbaum J . Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol. 2005; 140(3):509-16. PMC: 8935739. DOI: 10.1016/j.ajo.2005.03.057. View

Garweg J, Scherrer J, Halberstadt M . Recurrence characteristics in European patients with ocular toxoplasmosis. Br J Ophthalmol. 2008; 92(9):1253-6. DOI: 10.1136/bjo.2007.123661. View

Holland G, Crespi C, Dam-van Loon N, Charonis A, Yu F, Bosch-Driessen L . Analysis of recurrence patterns associated with toxoplasmic retinochoroiditis. Am J Ophthalmol. 2008; 145(6):1007-1013. DOI: 10.1016/j.ajo.2008.01.023. View

10.

Sibley L, Adams L, Fukutomi Y, Krahenbuhl J . Tumor necrosis factor-alpha triggers antitoxoplasmal activity of IFN-gamma primed macrophages. J Immunol. 1991; 147(7):2340-5. View

11.

Lahmar I, Abou-Bacar A, Abdelrahman T, Guinard M, Babba H, Ben Yahia S . Cytokine profiles in toxoplasmic and viral uveitis. J Infect Dis. 2009; 199(8):1239-49. DOI: 10.1086/597478. View

12.

Delair E, Creuzet C, Dupouy-Camet J, Roisin M . In vitro effect of TNF-alpha and IFN-gamma in retinal cell infection with Toxoplasma gondii. Invest Ophthalmol Vis Sci. 2009; 50(4):1754-60. DOI: 10.1167/iovs.07-1376. View

13.

Holland G . Ocular toxoplasmosis: the influence of patient age. Mem Inst Oswaldo Cruz. 2009; 104(2):351-7. DOI: 10.1590/s0074-02762009000200031. View

14.

Kortbeek L, Hofhuis A, Nijhuis C, Havelaar A . Congenital toxoplasmosis and DALYs in the Netherlands. Mem Inst Oswaldo Cruz. 2009; 104(2):370-3. DOI: 10.1590/s0074-02762009000200034. View

15.

Guiton R, Vasseur V, Charron S, Arias M, Van Langendonck N, Buzoni-Gatel D . Interleukin 17 receptor signaling is deleterious during Toxoplasma gondii infection in susceptible BL6 mice. J Infect Dis. 2010; 202(3):427-35. DOI: 10.1086/653738. View

16.

Norose K, Kikumura A, Luster A, Hunter C, Harris T . CXCL10 is required to maintain T-cell populations and to control parasite replication during chronic ocular toxoplasmosis. Invest Ophthalmol Vis Sci. 2010; 52(1):389-98. PMC: 3053287. DOI: 10.1167/iovs.10-5819. View

17.

Talabani H, Mergey T, Yera H, Delair E, Brezin A, Langsley G . Factors of occurrence of ocular toxoplasmosis. A review. Parasite. 2010; 17(3):177-82. DOI: 10.1051/parasite/2010173177. View

18.

Pleyer U, Ruokonen P . [Aqueous humor analysis: a diagnostic tool in intraocular inflammation]. Klin Monbl Augenheilkd. 2010; 227(12):953-60. DOI: 10.1055/s-0029-1245927. View

19.

Suzuki Y, Sa Q, Gehman M, Ochiai E . Interferon-gamma- and perforin-mediated immune responses for resistance against Toxoplasma gondii in the brain. Expert Rev Mol Med. 2011; 13:e31. PMC: 3372998. DOI: 10.1017/S1462399411002018. View

20.

Sauer A, Pfaff A, Villard O, Creuzot-Garcher C, Dalle F, Chiquet C . Interleukin 17A as an effective target for anti-inflammatory and antiparasitic treatment of toxoplasmic uveitis. J Infect Dis. 2012; 206(8):1319-29. DOI: 10.1093/infdis/jis486. View