Protective mucosal Th2 immune response against Toxoplasma gondii by murine mesenteric lymph node dendritic cells.
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.
Dimier-Poisson
Isabelle
I
UMR Université-INRA d'Immunologie Parasitaire et Vaccinologia, UFR des Sciences Pharmaceutiques, 37200 Tours, France. dimier@univ-tours.fr
Aline
Fleur
F
Mévélec
Marie-Noëlle
MN
Beauvillain
Céline
C
Buzoni-Gatel
Dominique
D
Bout
Daniel
D
D019264:Adoptive Transfer; D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood / Q000378:metabolism; D000953:Antigens, Protozoan / Q000008:administration & dosage; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000145:classification / Q000276:immunology*; D005260:Female; D006801:Humans; D018928:Immunity, Mucosal; D007071:Immunoglobulin A, Secretory / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood; D016130:Immunophenotyping; D066298:In Vitro Techniques; D007422:Intestines / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D008643:Mesentery; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000145:classification / Q000276:immunology*; D014122:Toxoplasma / Q000276:immunology* / Q000472:pathogenicity; D014124:Toxoplasmosis, Animal / Q000276:immunology
D000913:Antibodies, Protozoan; D000953:Antigens, Protozoan; D016207:Cytokines; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G