Tetraspanin-3 regulates protective immunity against Eimera tenella infection following immunization with dendritic cell-derived exosomes

Authors: CACHO, EMILIO - University Of Zaragoza; GALLEGO, MARGARITA - University Of Zaragoza; Lee, Sung; Lillehoj, Hyun; QUILEZ, JOAQUIN - University Of Zaragoza; LILLEHOJ, ERIK - University Of Maryland; SANCHEZ-ACEDO, CARIDAD - University Of Zaragoza

Submitted to: Vaccine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/25/2013
Publication Date: 12/30/2013
Publication URL: http://handle.nal.usda.gov/10113/58958
Citation: Cacho, E.D., Gallego, M., Lee, S.H., Lillehoj, H.S., Quilez, J., Lillehoj, E.P., Sanchez-Acedo, C. 2013. Tetraspanin-3 regulates protective immunity against Eimera tenella infection following immunization with dendritic cell-derived exosomes. Vaccine. 31(41):4668-74. doi: 10.1016/j.vaccine.2013.06.109.

Interpretive Summary: We need a novel strategy to reduce economic losses caused by intestinal parasites in poultry since the current method of controlling intestinal parasitic diseases using drugs and live parasite vaccines are not sustainable. In this study, ARS scientists collaborated with scientists in Spain to develop a novel vaccine to control intestinal parasites of poultry. They have identified small subcellular particles of parasites which can stimulate the host’s immunity against whole parasites. Furthermore, they demonstrated that these small particles can 1) be used as a novel vaccine against a major intestinal parasitic disease in poultry and 2) induce host immunity that protected young chickens against parasitic disease. These new findings will be useful for vaccine companies to design novel molecular vaccines against avian coccidiosis to mitigate the use of antibiotics.

Technical Abstract: The effects of immunization with dendritic cell (DC) exosomes, which had been incubated or non-incubated with an anti-tetraspanin-3 (Tspan-3) blocking antibody (Ab), were studied using an experimental model of Eimeria tenella avian coccidiosis. Purified exosomes from cecal tonsil and splenic DCs expressed Tspan-3 protein. Chickens injected with exosomes non-incubated with the blocking Ab and derived from cecal tonsil DCs preloaded in vitro with E. tenella Ag had Ag-immunostaining cells in the ceca, but not the spleen. Conversely, Ag-containing cells were found only in the spleen, but not the ceca, of chickens given splenic DC exosomes. However, in chickens that received exosomes incubated with the blocking Ab, Ag-containing cells were observed in both lymphoid organs following administration of exosomes from either DC population. After injection of exosomes non-incubated with the blocking Ab, greater numbers of cells secreting interleukin-2 (IL-2), IL-16, interferon-', and E. tenella-reactive Abs were observed in the cecal tonsils of chickens immunized with cecal DC exosomes compared with the spleen. By contrast, more cytokine-and Ab-producing cells were present in the spleen of chickens given splenic DC exosomes compared with the ceca. Incubation with the blocking Ab gave equal numbers of cytokine- and Ab-producing cells in the cecal tonsils and spleen regardless of the source of exosomes. Immunization with E. tenella Ag-loaded cecal tonsil DC exosomes increased in vivo resistance against subsequent E. tenella infection. Increased protection against infection following cecal DC exosome immunization was partially blocked by incubation of exosomes with Tspan-3 Ab. These results suggest that Tspan-3 regulates the tissue distribution, as well as cytokine and Ab production, following DC exosome administration, and that Tspan-3 partially controls in vivo protection against experimental E. tenella challenge infection following exosomal immunization.