Histopathology of murine toxoplasmosis under treatment with dialyzable leukocyte extract

BACKGROUND Dialyzable leukocyte extracts (DLEs) contain molecules smaller than 10 kDa with biological activity in receptor organisms. Primarily, they participate in the regulation of the Th1 immune response, which is essential for the control of several intracellular infections, such as toxoplasmosis. This disease is associated with congenital infection, encephalitis or systemic infections in immunocompromised individuals. The clinical course of this infection fundamentally depends on a well-regulated immune response and timely treatment with the appropriate drugs. OBJECTIVE The aim of this study was to evaluate the effect of treatment with a leukocyte extract, derived from crocodile lymphoid tissue, on the histopathology and brain parasite load in NIH mice that had been infected with cysts of Toxoplasma gondii (ME-49 strain). METHODS The treatment was applied during the acute and chronic stages of the infection. Histopathological changes were evaluated in the ileum, liver and spleen at one, four and eight weeks after infection and in the brain at week 8. The parasite load was evaluated by counting the cysts of T. gondii found in the brain. FINDINGS Compared to the control mouse group, the mice infected with T. gondii and under treatment with DLE showed less tissue damage, mainly at the intestinal, splenic and hepatic levels. In addition, a greater percentage of survival was observed, and there was a considerable reduction in the parasite load in the brain. CONCLUSIONS The results suggest that DLE derived from crocodile is a potential adjunctive therapy in the conventional treatment of toxoplasmosis.

[1]  A. Daryani,et al.  Activities of anti-Toxoplasma drugs and compounds against tissue cysts in the last three decades (1987 to 2017), a systematic review , 2018, Parasitology Research.

[2]  D. Schlüter,et al.  Toxoplasma gondii‐induced neuronal alterations , 2015, Parasite immunology.

[3]  T. Inder,et al.  Infection-induced inflammation and cerebral injury in preterm infants. , 2014, The Lancet. Infectious diseases.

[4]  S. Daduang,et al.  Purification and Characterization of Antioxidant Peptides from Leukocyte Extract of Crocodylus siamensis , 2014, The Protein Journal.

[5]  Y. Takashima,et al.  Toxoplasma gondii tachyzoite-infected peripheral blood mononuclear cells are enriched in mouse lungs and liver. , 2013, Experimental parasitology.

[6]  Charlotte E. Egan,et al.  Insights into inflammatory bowel disease using Toxoplasma gondii as an infectious trigger , 2012, Immunology and cell biology.

[7]  C. Ware,et al.  Infection with Toxoplasma gondii Alters Lymphotoxin Expression Associated with Changes in Splenic Architecture , 2012, Infection and Immunity.

[8]  F. Martínez-Gómez,et al.  The intraperitoneal inoculation of Lactobacillus casei in mice induces total protection against Trichinella spiralis infection at low challenge doses , 2011, Parasitology Research.

[9]  D. Spray,et al.  Acquired infection with Toxoplasma gondii in adult mice results in sensorimotor deficits but normal cognitive behavior despite widespread brain pathology. , 2010, Microbes and infection.

[10]  Z. Ševčíková,et al.  Immune response of mice with alveolar echinococcosis to therapy with transfer factor, alone and in combination with albendazole , 2009, Parasitology Research.

[11]  R. Mondragón-Flores,et al.  Protection against Toxoplasma gondii brain cyst formation in mice immunized with Toxoplasma gondii cytoskeleton proteins and Lactobacillus casei as adjuvant. , 2009, Veterinary parasitology.

[12]  O. Liesenfeld,et al.  Small intestinal inflammation following oral infection with Toxoplasma gondii does not occur exclusively in C57BL/6 mice: review of 70 reports from the literature. , 2009, Memorias do Instituto Oswaldo Cruz.

[13]  D. Gutmann,et al.  Astrocyte gp130-expression is critical for the control of Toxoplasma encephalitis , 2008, Journal of immunology.

[14]  G. Yap,et al.  Cytokine regulation of immunopathology in toxoplasmosis , 2007, Immunology and cell biology.

[15]  R. Ptak,et al.  Broad spectrum antimicrobial activity of leukocyte extracts from the American alligator (Alligator mississippiensis). , 2006, Veterinary immunology and immunopathology.

[16]  X. Zhan,et al.  Preparation and determination of immunological activities of anti-HBV egg yolk extraction. , 2006, Cellular & molecular immunology.

[17]  J. Schwartzman,et al.  Interleukin-17/Interleukin-17 Receptor-Mediated Signaling Is Important for Generation of an Optimal Polymorphonuclear Response against Toxoplasma gondii Infection , 2005, Infection and Immunity.

[18]  R. Hernández-Pando,et al.  Transfer factors as immunotherapy and supplement of chemotherapy in experimental pulmonary tuberculosis , 2004, Clinical and experimental immunology.

[19]  C. Hunter,et al.  The role of astrocytes in the immunopathogenesis of toxoplasmic encephalitis. , 2004, International journal for parasitology.

[20]  L. Weiss,et al.  Toxoplasma gondii: from animals to humans. , 2000, International journal for parasitology.

[21]  C. Kirkpatrick.  Transfer Factors: Identification of Conserved Sequences in Transfer Factor Molecules , 2000, Molecular medicine.

[22]  Y. Suzuki,et al.  Association of CD4+ T cell-dependent, interferon-gamma-mediated necrosis of the small intestine with genetic susceptibility of mice to peroral infection with Toxoplasma gondii , 1996, The Journal of experimental medicine.

[23]  D. Graham,et al.  Pathological changes in the brains of mice infected with Toxoplasma gondii: a histological, immunocytochemical and ultrastructural study. , 1991, International journal of experimental pathology.

[24]  O. Delgado,et al.  Dialyzable leukocyte extract therapy in immunodepressed patients with cutaneous leishmaniasis. , 1981, Clinical immunology and immunopathology.

[25]  H. Lawrence,et al.  The transfer in humans of delayed skin sensitivity to streptococcal M substance and to tuberculin with disrupted leucocytes. , 1955, The Journal of clinical investigation.

[26]  I. Estrada-García,et al.  Adjuvant treatment with a dialyzable leukocytes extract contributes to maintain HPV-infected women free of low-grade cervical lesions. , 2015, European journal of gynaecological oncology.

[27]  S. Daduang,et al.  Comparisons of Anti-inflammatory Activity of Crocodile ( Crocodylus siamensis ) Blood Extract , 2014 .

[28]  Dolores Javier Sánchez González,et al.  Factores de transferencia en la terapéutica médica , 2011 .

[29]  F. E. Espinosa Rosales,et al.  [Effect of transfer factor on treatment with glucocorticoids in a group of pediatric patients with persistent moderate allergic asthma]. , 2009, Revista alergia Mexico.

[30]  M. Franco-Molina,et al.  IMMUNEPOTENT CRP (bovine dialyzable leukocyte extract) adjuvant immunotherapy: a phase I study in non-small cell lung cancer patients. , 2008, Cytotherapy.

[31]  A. Capron,et al.  Infection with Toxoplasma gondii RH and Prugniaud strains in mice, rats and nude rats: kinetics of infection in blood and tissues related to pathology in acute and chronic infection. , 1999, Pathology, research and practice.