Mast Cells Modulate Acute Toxoplasmosis in Murine Models

Bo Huang,Lloyd H Kasper,Huanqin Zheng,Yong Wang,Fangli Lu,Ying Chen,Jilong Shen,Shiguang Huang,Zhao-Rong Lun,Markus M Heimesaat

doi:10.1371/journal.pone.0077327

Abstract

The role of mast cells (MCs) in Toxoplasma gondii infection is poorly known. Kunming outbred mice were infected intraperitoneally with RH strain T. gondii, either treated with compound 48/80 (C48/80, MC activator) or disodium cromoglycate (DSCG, MC inhibitor). Compared with infected controls, infected mice treated with C48/80 exhibited significantly increased inflammation in the liver (P < 0.01), spleen (P < 0.05), and mesentery (P < 0.05) tissues, higher parasite burden in the peritoneal lavage fluids (P < 0.01), and increased levels of mRNA transcripts of T. gondii tachyzoite surface antigen 1 (SAG1) gene in the spleen and liver tissues (P < 0.01), accompanied with significantly increased Th1 cytokine (IFN-γ, IL-12p40, and TNF-α) (P < 0.01) and decreased IL-10 (P < 0.01) mRNA expressions in the liver, and increased IFN-γ (P < 0.01) and IL-12p40 (P < 0.01) but decreased TNF-α (P < 0.01) and IL-4 (P < 0.01) in the spleens of infected mice treated with C48/80 at day 9-10 p.i. Whereas mice treated with DSCG had significantly decreased tissue lesions (P < 0.01), lower parasite burden in the peritoneal lavage fluids (P < 0.01) and decreased SAG1 expressions in the spleen and liver tissues (P < 0.01), accompanied with significantly increased IFN-γ (P < 0.01) and IL-12p40 (P < 0.05) in the liver, and decreased IFN-γ (P < 0.05) and TNF-α (P < 0.01) in the spleens; IL-4 and IL-10 expressions in both the spleen and liver were significantly increased (P < 0.01) in the infected mice treated with DSCG. These findings suggest that mediators associated with the MC activation may play an important role in modulating acute inflammatory pathogenesis and parasite clearance during T. gondii infection in this strain of mice. Thus, MC activation/inhibition mechanisms are potential novel targets for the prevention and control of T. gondii infection.

Highlights

Toxoplasma gondii is a common and significant obligate intracellular pathogen of humans and animals, which infects nearly one third of the human population and is found in an extraordinary range of vertebrate hosts [1]
We assessed the role of Mast cells (MCs) during acute murine T. gondii infection; our findings suggest that release of mediators after MC activation plays an important role in modulating inflammatory pathogenesis and parasite load during acute T. gondii infection
MCs were intact in uninfected (Figures 2e, 3e, 4e, and 5e) and T. gondii-infected mice (Figures 2f, 3f, 4f, and 5f) with disodium cromoglycate (DSCG) treatment, and the latter appeared morphologically indistinguishable from the uninfected controls

Summary

Introduction

Toxoplasma gondii is a common and significant obligate intracellular pathogen of humans and animals, which infects nearly one third of the human population and is found in an extraordinary range of vertebrate hosts [1]. The immune/ inflammatory response to T. gondii infection is essential to control parasite replication and tissue spread and can cause tissue damage, being decisive to pathogenesis [2]. MCs have been described as essential effector cells of immediate hypersensitivity and chronic allergic reactions that contribute to asthma, atopic dermatitis, and other allergic diseases [4]. Recent findings indicate that MCs are more functionally diverse than previously described. MCs play a role in many different processes, and they are involved in responses against pathogenic infections and most notably in connection with innate immune responses, wound healing, and inflammatory disease [7]. Recent studies indicate that MCs are involved in immune regulation [8,9]

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Conclusion