Protective Mucosal Th2 Immune Response againstToxoplasma gondiiby Murine Mesenteric Lymph Node Dendritic Cells

Abstract

Toxoplasma gondii, an obligate intracellular parasite pathogen which initially invades the intestinal epithelium before disseminating throughout the body, may cause severe sequelae in fetuses and life-threatening neuropathy in immunocompromised patients. Immune protection is usually thought to be performed through a systemic Th1 response; considering the route of parasite entry it is important to study and characterize the local mucosal immune response to T. gondii. Despite considerable effort, Toxoplasma-targeted vaccines have proven to be elusive using conventional strategies. We report the use of mesenteric lymph node dendritic cells (MLNDCs) pulsed ex vivo with T. gondii antigens (TAg) as a novel investigation approach to vaccination against T. gondii-driven pathogenic processes. Using a murine model, we demonstrate in two genetically distinct mouse strains (C57BL/6 and CBA/J) that adoptively transferred TAg-pulsed MLNDCs elicit a mucosal Toxoplasma-specific Th2-biased immune response in vivo and confer strong protection against infection. We also observe that MLNDCs mostly traffic to the intestine where they enhance resistance by reduction in the mortality and in the number of brain cysts. Thus, ex vivo TAg-pulsed MLNDCs represent a powerful tool for the study of protective immunity to T. gondii, delivered through its natural route of entry. These findings might impact the design of vaccine strategies against other invasive microorganisms known to be delivered through digestive tract.

A comparative study between excretory/secretory and autoclaved vaccines against RH strain of Toxoplasma gondii in murine models

“…The survival time extended up to 15th days (mean of survival = 11.5 days) in ATV vaccinated group and highly significant difference was found between survival curves of ATV vaccinated group and both control groups, these results agreed with the results of Eissa et al (2012) who suggested that significant immune responses were developed following vaccination with ATV as demonstrated by the delayed death of vaccinated mice following RH challenge by nine days. The survival time extended up to 16th days (mean of survival = 12.7 days) in ESA vaccinated group post infection, highly significant difference was found between survival curves of ESA vaccinated group and both control groups, agreeing with extended survival time with ESA up to 15th days reported by Daryani et al (2003).…”

“…Ali et al (2003) reported decreased pathological changes following vaccination by live cyst vaccines and irradiated cyst vaccine. Even though the tachyzoite challenge was lethal to the mice, it can be concluded that ESA vaccine showed more promising results versus ATV, as demonstrated by the survival rate of vaccinated mice; tachyzoites count and histopathological examination, this could be attributed to the fact that ESA of T. gondii tachyzoites, represent more than 90 % of the parasite circulating antigens, might be the first target of the host immune system (Daryani et al 2003).…”

“…As Toxoplasma secretion is an important event in the production of circulating antigens during the early stages of toxoplasmosis (Hughes and Vanknapen 1982), ESA was shown to be highly immunogenic (Saadatnia et al 2012). ESA might be one of the first targets for the immune system; the protective potentialities of ESA would suggest an alternative approach for vaccine development (Daryani et al 2003).…”

“…Zenner et al (1999) have reported that purified ESA, namely GRA2 and GRA5, had a significant degree of organs' protection. Furthermore, a study conducted by Daryani et al (2003) showed that the ESA-F2 antigens could be used as a good candidate for the development of new immunization strategy against toxoplasmosis.…”

“…The ESA can stimulate a better cell-mediated immune response as compared to soluble or cyst antigens, therefore, ESA antigen is an excellent candidate for research as immunizing agents against T. gondii infection (Rahman and Anuar 1992). Daryani et al (2003) compared between, Total lysate antigen and ESA-fractions and they suggested that ESA-F2 could be used as a good candidate for the development of new immunization strategy against toxoplasmosis.…”