Immune profiling of pregnant Toxoplasma-infected US and Colombia patients reveals surprising impacts of infection on peripheral blood cytokines

Abstract

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.

Keywords: Colombia; Toxoplasma gondii; acute; chronic; congenital, cytokine profile; cytokines; pregnant; toxoplasmosis.

Figure 1.

Cytokine profiling of infected US cohorts. A, Median florescent intensity (MFI) values (y-axis) represent the ratio of the average MFI per cytokine between acute and uninfected, and chronic and uninfected pregnant US women. All cytokines shown had statistical significance for the acute to uninfected comparison (P < .05 at FDR 5%). Nine cytokines (denoted by ^§) also had a raw P value < .05 for the chronic to uninfected comparison, although none were significant (P < .05) between these 2 groups using the more stringent test of having the FDR set at 5%. Dotted line at 1 represents no difference in MFI values between uninfected and infected cohorts. B, MFI values (y-axis) reported for all cohorts (x-axis): Uninfected (U), Acute (A), and Chronic (C) for those cytokines found to be significantly different between uninfected and acutely infected cohorts. Abbreviation: FDR, false discovery rate.

Figure 2.

Cytokine profiling of infected Colombian cohorts. A, MFI values (y-axis) represent the ratio of the average MFI per cytokine between acute and uninfected, and chronic and uninfected pregnant Colombian women. All cytokines shown had statistical significance for the acute to uninfected comparison (raw P < .05). Eight cytokines (denoted by *) were also significant (P < .05) using the more stringent test where the FDR is set to 5%. No significant differences were detected between the chronic and uninfected cohorts. Dotted line at 1 represents no difference in MFI values between uninfected and infected cohorts. B, MFI values (y-axis) reported for all cohorts (x-axis): Uninfected (U), Acute (A), and Chronic (C) for those cytokines found to be significantly different between uninfected and acutely infected cohorts. Abbreviations: FDR, false discovery rate; MFI, median florescent intensity.

Figure 3.

Schematic of cytokines significantly dysregulated between US acute, US chronic, and Colombian acute cohorts in comparison to uninfected cohorts sampled within the same country. All cytokines significant in any pair-wise combination (P < .05), either with the more stringent FDR of 5% (for the US samples) or a raw P value < .05 (for the Colombian cohort) were included. Arrows and arrowheads indicate the difference relative to uninfected controls in the US and Colombian cohorts, respectively. Abbreviation: FDR, false discovery rate.