Cytokine profiling reveals decreased serum levels of CCL2 in active ocular toxoplasmosis

Rey, Amanda; Molins, Blanca; Llorenç, Víctor; Pelegrín, Laura; Mesquida, Marina; Adán, Alfredo

doi:10.1136/bjophthalmol-2013-303092

Cited by 7 publications

(6 citation statements)

References 28 publications

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“…Above all, it suggests that severity may be a key variable for subgrouping ME/CFS. Furthermore, the levels of circulating cytokines in response to inflammatory triggers such as infection have been reported by various groups to be lower than in controls for some cytokines and higher for others (34)(35)(36). A response with lower levels of cytokines may represent a down-regulatory effort by the immune system in an attempt to attenuate more severe immunopathology, resulting in milder or even no symptomatology.…”

Section: Discussionmentioning

confidence: 99%

Cytokine signature associated with disease severity in chronic fatigue syndrome patients

Montoya

Holmes

Anderson

et al. 2017

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

308

265

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Although some signs of inflammation have been reported previously in patients with myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS), the data are limited and contradictory. High-throughput methods now allow us to interrogate the human immune system for multiple markers of inflammation at a scale that was not previously possible. To determine whether a signature of serum cytokines could be associated with ME/CFS and correlated with disease severity and fatigue duration, cytokines of 192 ME/CFS patients and 392 healthy controls were measured using a 51-multiplex array on a Luminex system. Each cytokine’s preprocessed data were regressed on ME/CFS severity plus covariates for age, sex, race, and an assay property of newly discovered importance: nonspecific binding. On average, TGF-β was elevated (P = 0.0052) and resistin was lower (P = 0.0052) in patients compared with controls. Seventeen cytokines had a statistically significant upward linear trend that correlated with ME/CFS severity: CCL11 (Eotaxin-1), CXCL1 (GROα), CXCL10 (IP-10), IFN-γ, IL-4, IL-5, IL-7, IL-12p70, IL-13, IL-17F, leptin, G-CSF, GM-CSF, LIF, NGF, SCF, and TGF-α. Of the 17 cytokines that correlated with severity, 13 are proinflammatory, likely contributing to many of the symptoms experienced by patients and establishing a strong immune system component of the disease. Only CXCL9 (MIG) inversely correlated with fatigue duration.

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Section: Discussionmentioning

confidence: 99%

Cytokine signature associated with disease severity in chronic fatigue syndrome patients

Montoya

Holmes

Anderson

et al. 2017

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

308

265

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“…Women who had a suspected or confirmed diagnosis of T. gondii infection during pregnancy prior to being enrolled in the epidemiological study were excluded from the group studied here. Sera for our study were from 50 consecutive uninfected women (average age 29; range 17-46), 50 consecutive chronically infected women (average age 29; range , and 13 consecutive acutely infected women (average age 27; range [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36]. As for the US patients, gestational age was not systematically obtained.…”

Section: Colombian Patientsmentioning

confidence: 99%

Immune Profiling of Pregnant Toxoplasma-Infected US and Colombia Patients Reveals Surprising Impacts of Infection on Peripheral Blood Cytokines

Pernas

Ramirez²,

Holmes

et al. 2014

The Journal of Infectious Diseases

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In North America (NA) and Europe, the majority of toxoplasmosis cases are benign and generally asymptomatic, whereas in South America (SA) toxoplasmosis is associated with much more severe symptoms in adults and congenitally infected children. The reasons for these differences remain unknown; currently, there is little information from patients in either region on how the immune system responds to infection with Toxoplasma gondii. Here, we report the relative abundance of 51 serum cytokines from acute and chronic toxoplasmosis cohorts of pregnant women from the United States, where approximately one-half of clinical isolates are Type II, and Colombia, where clinical isolates are generally "atypical" or Type I-like strains. Surprisingly, the results showed notably lower levels of 23 cytokines in acutely infected patients from the United States, relative to uninfected US controls. In acutely infected Colombian patients, however, only 8 cytokine levels differed detectably with 4 being lower and 4 higher relative to uninfected controls. Strikingly, there were also differences in the cytokine profiles of the chronically infected patients relative to uninfected controls in the US cohort. Hence, Toxoplasma appears to specifically impact levels of circulating cytokines, and our results may partly explain region-specific differences in the clinical spectrum of toxoplasmosis.

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“…40 In serum, IL-6 levels have been reported to increase during the acute-phase 22,46,63,66,67 and decrease thereafter 22,66 or to not differ from baseline levels or not differ between phases. 39,44,78 These data indicate that IL-6 in the AH plays a crucial role in the immunopathogenesis of active OT and that IL-6 in the AH but not in the serum might be an indicator of disease status.…”

Section: Discussionmentioning

confidence: 85%

“…44,62 However, some reports show opposing findings: the serum level of CCL2/MCP-1 was significantly lower in patients with active OT than in healthy subjects, which suggests that a reduced serum level of CCL2/MCP-1 is associated with active OT and could be used as a marker of disease activity. 78 In HIV-infected patients, the levels of these chemokines were not increased in the CSF. 26 G-CSF contributes to the robust proinflammatory response induced by T. gondii infection.…”

Section: Discussionmentioning

confidence: 94%

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

Xue

Hikosaka

et al. 2021

Invest. Ophthalmol. Vis. Sci.

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PURPOSE. To establish a murine model of primary acquired ocular toxoplasmosis (OT) and to investigate the immune mediator profiles in the aqueous humor (AH). METHODS. C57BL/6 mice were perorally infected with Toxoplasma gondii. The ocular fundus was observed, and fluorescein angiography (FA) was performed. The AH, cerebrospinal fluid (CSF), and serum were collected before infection and at 28 days postinfection (dpi); the immune mediator levels in these samples were analyzed using multiplex bead assay. RESULTS. Fundus imaging revealed soft retinochoroidal lesions at 14 dpi; many of these lesions became harder by 28 dpi. FA abnormalities, such as leakage from retinal vessels and dilation and tortuosity of the retinal veins, were observed at 14 dpi. Nearly all these abnormalities resolved spontaneously at 28 dpi. In the AH, interferon-γ , interleukin (IL)-1α, IL-1β, IL-6, IL-10, IL-12(p40), IL-12(p70), CCL2/MCP-1, CCL3/MIP-1α, CCL4/MIP-1β, CCL5/RANTES, and CXCL1/KC levels increased after infection. All these molecules except IL-1α, IL-4, and IL-13 showed almost the same postinfection patterns in the CSF as they did in the AH. The tumor necrosis factor α, IL-4, and IL-5 levels in the AH and CSF of the T. gondii-infected mice were lower than those in the serum. The postinfection IL-1α, IL-6, CCL2/MCP-1, CCL4/MIP-1β, and granulocyte colony-stimulating factor levels in the AH were significantly higher than those in the CSF and serum. CONCLUSIONS. A murine model of primary acquired OT induced via the natural infection route was established. This OT model allows detailed ophthalmologic, histopathologic, and immunologic evaluations of human OT. Investigation of AH immune modulators provides new insight into OT immunopathogenesis.

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Cytokine profiling reveals decreased serum levels of CCL2 in active ocular toxoplasmosis

Abstract: Decreased serum levels of CCL2 may be associated with active ocular toxoplasmosis and could therefore serve as a marker of disease activity.

Cited by 7 publications

References 28 publications

Cytokine signature associated with disease severity in chronic fatigue syndrome patients

Cytokine signature associated with disease severity in chronic fatigue syndrome patients

Immune Profiling of Pregnant Toxoplasma-Infected US and Colombia Patients Reveals Surprising Impacts of Infection on Peripheral Blood Cytokines

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

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