Immunosuppression with cyclophosphamide favors reinfection with recombinantToxoplasma gondiistrains

L.A Silva,G.P Brandão,B.V Pinheiro,R.W.A Vitor

doi:10.1051/parasite/2012193249

L.A Silva, G.P Brandão + Show 2 more

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https://doi.org/10.1051/parasite/2012193249

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Abstract

The aim of this study was to verify the effect of immunosuppression by cyclophosphamide (Cy) on susceptibility of BALB/c mice subjected to challenge with recombinant strains of Toxoplasma gondii. Animals were prime infected with the D8 (recombinant I/III) or the ME49 (type II) non-virulent strains, weekly immunosuppressed with Cy and challenged with the CH3 or EGS virulent strains (I/III). Parasites recovered from surviving mice were submitted to PCR-RFLP analysis to confirm co-infection. Prime-infection with the D8 strain conferred more protection against challenge with the CH3 and EGS strains when compared with ME49 prime infection. Cy treatment caused significant leukopenia in the infected mice, what probably favors reinfection after challenge. Reinfection was associated with increased levels of IgA. Otherwise, Cy-treated mice presented significantly lower IgA levels after challenge, suggesting involvement of this immunoglobulin on protection against reinfection. In conclusion, BALB/c mice susceptibility to reinfection by T. gondii is related to genetic differences among the strains used for primary and challenge infections. Alteration of the host’s immune integrity by Cy probably compromises the protection previously established by primary infection.

Highlights

Toxoplasma gondii is an obligate intracellular parasite distributed worldwide, capable of infecting all the homeothermic animals
Naive: mice without infection. c Number of survivors (n) out of the total number of mice challenged (N). d Mean number of brain cysts evaluated 30 days post challenge. e Number of mice presenting the two strains (n) out of the total number of survivors after challenge (N). f Significant difference between mice primary infected with the D8 strain and challenged with the EGS strain and mice primary infected with the D8 strain, Cy-immunosuppressed and challenged with the EGS strain, p < 0.05. g Significant difference between mice primary infected with the ME49 strain and challenged with the EGS strain and mice primary infected with the ME49 strain, p < 0.05
The number of brain cysts in non-immunosuppressed mice primary infected with the ME49 strain and challenged with the EGS strain, significantly increased compared to the non-challenged mice

Summary

Introduction

Toxoplasma gondii is an obligate intracellular parasite distributed worldwide, capable of infecting all the homeothermic animals. The immunity acquired by primary infection with T. gondii was Parasite, 2012, 19, 249-257. & VITOR R.W.A. ting the process of reinfection in immunosuppressed animal models are currently available. Cyclophosphamide (Cy) has been used in the treatment of several types of cancer. Because it presents immunosuppressing properties, it has been used in the treatment of autoimmune diseases, non-specific immunopathies, and to prevent transplant rejection (Allison, 2000; Emadi et al, 2009). This study aimed to evaluate the interference of the genotypic differences in the process of reinfection by recombinant strains of T. gondii in Cy-immunosuppressed mouse model

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