Long-Term Impact of Toxoplasma gondii Infection on Human Monocytes.

Hauke G Ehmen,Carsten G K Lüder

doi:10.3389/fcimb.2019.00235

Hauke G Ehmen, Carsten G K Lüder

Open Access

https://doi.org/10.3389/fcimb.2019.00235

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Abstract

Toxoplasma gondii is a prevalent parasite of mammals and birds including up to 30% of humans world-wide. Primary infection of immunocompetent hosts leads to a robust cell-mediated immune response, which controls but does not clear the infection, thus enabling long-term parasite persistence in brain and muscle tissues. Chronic toxoplasmosis in mice is associated with resistance to heterologous pathogens and this has been related to increased numbers of inflammatory monocytes. Here we have analyzed whether chronic T. gondii infection impacts the subset distribution and the phenotype of peripheral human monocytes in vivo and their responses to parasite infection in vitro. CD14+ monocytes from T. gondii-seropositive blood donors expressed significantly less FcγRIII (CD16) than those from seronegative controls, but they did not show a shift in the distribution of classical, intermediate and non-classical monocyte subpopulations. Percentages of CD62L+ and CD64+ monocytes were however decreased and increased, respectively, in chronically infected individuals as compared to naïve controls. Infection of monocyte-enriched PBMCs from both seropositive and seronegative individuals with T. gondii led to an increase of CD14+CD16− classical monocytes and a decrease of CD14+CD16+ double positive monocytes. Remarkably, after in vitro parasite infection, expression of the chemokine receptor CCR2 was severely impaired in monocytes from both, individuals with chronic toxoplasmosis and seronegative controls. In contrast, only monocytes from chronically infected humans but not those from controls dose-dependently up-regulated HLA-DR, DP, DQ expression following in vitro infection. Furthermore, monocyte-enriched PBMCs from seropositive individuals up-regulated IL-12 mRNA more vigorously after in vitro infection than cells from naïve controls. Collectively, our results establish that infection of humans with T. gondii exerts long-term effects on the phenotype and responsiveness of blood monocytes. This may have important implications for innate immune responses to T. gondii and unrelated pathogens.

Highlights

The intracellular parasite Toxoplasma gondii is widespread in birds and mammals including an estimated 30% of humans world-wide
The results revealed a dramatic expansion of CD14+CD16− monocytes after parasite infection in vitro with a concomitant increase of CD64 expression but a strong decrease of CCR2
Chronic human infection underlies lifethreatening reactivated toxoplasmosis in immunocompromised patients (Montoya and Liesenfeld, 2004), recrudescent ocular toxoplasmosis in immunocompetent individuals (Pleyer et al, 2014), and it has been associated with several psychiatric disorders (Sutterland et al, 2015) and behavioral changes (Flegr et al, 2002)

Summary

Introduction

The intracellular parasite Toxoplasma gondii is widespread in birds and mammals including an estimated 30% of humans world-wide. Infections of immunocompetent hosts are mostly asymptomatic or benign but they lead to parasite persistence for months to years and possibly even for the hosts’ life. Reactivation of chronic toxoplasmosis in immunocompromised individuals, Monocytes During Chronic Human Toxoplasmosis e.g., those with AIDS or under immunosuppressive therapy, can lead to necrotizing tissue damage and lifethreatening Toxoplasma encephalitis (Montoya and Liesenfeld, 2004). Primary infection of pregnant women can lead to intrauterine transmission with severe symptoms or even death of the fetus or significant sequelae after birth. Human toxoplasmosis has been recognized as one of the leading food-borne infectious diseases in the USA based on annual costs and loss of quality-adjusted life years (Hoffmann et al, 2012)

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