{"id":{"repo_id":"wustl","oai_identifier":"oai:openscholarship.wustl.edu:etd-2054"},"canonical_url":"https://search.dev.ndltd.org/etd/wustl/oai:openscholarship.wustl.edu:etd-2054","repository":{"repo_id":"wustl","name":"Washington University in St. Louis","base_url":"https://openscholarship.wustl.edu/do/oai/"},"display":{"title":"Batf3-Deficient Mice: Susceptibility to Toxoplasma gondii and Responses to IL-12 Treatment in vivo","abstract":"

CD8α+ dendritic cells are important in vivo for cross-presentation of antigens derived from intracellular pathogens and tumors. Additionally, stimulation of IL-12 production by CD8α+ DCs has suggested a role for these cells in response to Toxoplasma gondii antigens, although no experiments have yet shown an in vivo requirement for these cells against T. gondii infection. Towards this goal, we examined T. gondii infection of Batf3-/- mice, which selectively lack only lymphoid-resident CD8α+ DCs and related peripheral CD103+ DCs. Batf3-/- mice were extremely susceptible to T. gondii infection, with defective priming of CD8+ T cells, and decreased production of IL-12 and IFNγ. IL-12 administration restored resistance in Batf3-/- mice, and mice in which IL-12 production was ablated only from CD8α+ DCs failed to control infection. These results reveal that the function of CD8α+ DCs extends beyond a role in cross-presentation and includes a critical role for activation of innate immunity through IL-12 production during T. gondii infection.

While investigating the immune responses of Batf3-/- mice to T. gondii infection, we made the surprising discovery that IL-12 treatment of infected Batf3-/- mice resulted in re-appearance of the CD8α+ DC population in the spleen. In addition, we show that IL-12-treatment alone in the absence of infection restored the CD8α+ DC population in Batf3-/- mice. Analysis of the restored cells by microarray revealed very few differences in gene expression between wild-type and IL-12-induced Batf3-/- CD8α+ DCs. Furthermore, IL-12 treatment of Batf3-/- mice restored their capacity for in vivo cross-presentation of necrotic cell-associated antigens. Finally, the restored CD8α+ DCs primed CD8+ T cells against T. gondii-derived antigen, and produced IL-12 in vivo in response to T. gondii infection. Thus, IL-12 can induce development of CD8α+ DCs through a Batf3-independent mechanism, and these cells can function to both prime T cells as well as produce IL-12 during infection in vivo.

","abstract_html":"<p>CD8&alpha;<super>+</super> dendritic cells are important <italic>in vivo</italic> for cross-presentation of antigens derived from intracellular pathogens and tumors. Additionally, stimulation of IL-12 production by CD8&alpha;<super>+</super> DCs has suggested a role for these cells in response to <italic>Toxoplasma gondii</italic> antigens, although no experiments have yet shown an <italic>in vivo</italic> requirement for these cells against <italic>T. gondii</italic> infection. Towards this goal, we examined <italic>T. gondii</italic> infection of Batf3<super>-/-</super> mice, which selectively lack only lymphoid-resident CD8&alpha;<super>+</super> DCs and related peripheral CD103<super>+</super> DCs. Batf3<super>-/-</super> mice were extremely susceptible to <italic>T. gondii</italic> infection, with defective priming of CD8<super>+</super> T cells, and decreased production of IL-12 and IFN&gamma;. IL-12 administration restored resistance in Batf3<super>-/-</super> mice, and mice in which IL-12 production was ablated only from CD8&alpha;<super>+</super> DCs failed to control infection. These results reveal that the function of CD8&alpha;<super>+</super> DCs extends beyond a role in cross-presentation and includes a critical role for activation of innate immunity through IL-12 production during <italic>T. gondii</italic> infection.</p><p>While investigating the immune responses of Batf3<super>-/-</super> mice to <italic>T. gondii</italic> infection, we made the surprising discovery that IL-12 treatment of infected Batf3<super>-/-</super> mice resulted in re-appearance of the CD8&alpha;<super>+</super> DC population in the spleen. In addition, we show that IL-12-treatment alone in the absence of infection restored the CD8&alpha;<super>+</super> DC population in Batf3<super>-/-</super> mice. Analysis of the restored cells by microarray revealed very few differences in gene expression between wild-type and IL-12-induced Batf3<super>-/-</super> CD8&alpha;<super>+</super> DCs. Furthermore, IL-12 treatment of Batf3<super>-/-</super> mice restored their capacity for <italic>in vivo</italic> cross-presentation of necrotic cell-associated antigens. Finally, the restored CD8&alpha;<super>+</super> DCs primed CD8<super>+</super> T cells against <italic>T. gondii</italic>-derived antigen, and produced IL-12 <italic>in vivo</italic> in response to <italic>T. gondii</italic> infection. Thus, IL-12 can induce development of CD8&alpha;<super>+</super> DCs through a Batf3-independent mechanism, and these cells can function to both prime T cells as well as produce IL-12 during infection <italic>in vivo</italic>.</p>","abstract_has_math":false,"creators":["Mashayekhi, Mona"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation","degree_discipline":"Biology and Biomedical Sciences: Immunology","degree_department":null,"school":null,"contributors":["Kenneth M Murphy"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-03-04T08:00:00Z","date_published":"2013-03-04T08:00:00Z","updated_at":"2026-07-24T06:13:31Z","subjects":["Batf3","CD8-alpha+ dendritic cells","IL-12","Toxoplasma gondii","Immunology and Infectious Disease"],"languages":["English (en)"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.7936/K7RJ4GG5"],"render_values":[{"text":"https://doi.org/10.7936/K7RJ4GG5","href":"https://doi.org/10.7936/K7RJ4GG5","code":true}]}]},"links":{"outbound_url":"https://openscholarship.wustl.edu/etd/1054","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Kenneth M Murphy"]},{"key":"dc:creator","label":"Author","values":["Mashayekhi, Mona"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2013-08-26T07:00:00Z"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Biology and Biomedical Sciences: Immunology"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Batf3","CD8-alpha+ dendritic cells","IL-12","Toxoplasma gondii","Immunology and Infectious Disease"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English (en)"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://openscholarship.wustl.edu/etd/1054"]},{"key":"dc:identifier.doi","label":"DOI","values":["https://doi.org/10.7936/K7RJ4GG5"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["

CD8α+ dendritic cells are important in vivo for cross-presentation of antigens derived from intracellular pathogens and tumors. Additionally, stimulation of IL-12 production by CD8α+ DCs has suggested a role for these cells in response to Toxoplasma gondii antigens, although no experiments have yet shown an in vivo requirement for these cells against T. gondii infection. Towards this goal, we examined T. gondii infection of Batf3-/- mice, which selectively lack only lymphoid-resident CD8α+ DCs and related peripheral CD103+ DCs. Batf3-/- mice were extremely susceptible to T. gondii infection, with defective priming of CD8+ T cells, and decreased production of IL-12 and IFNγ. IL-12 administration restored resistance in Batf3-/- mice, and mice in which IL-12 production was ablated only from CD8α+ DCs failed to control infection. These results reveal that the function of CD8α+ DCs extends beyond a role in cross-presentation and includes a critical role for activation of innate immunity through IL-12 production during T. gondii infection.

While investigating the immune responses of Batf3-/- mice to T. gondii infection, we made the surprising discovery that IL-12 treatment of infected Batf3-/- mice resulted in re-appearance of the CD8α+ DC population in the spleen. In addition, we show that IL-12-treatment alone in the absence of infection restored the CD8α+ DC population in Batf3-/- mice. Analysis of the restored cells by microarray revealed very few differences in gene expression between wild-type and IL-12-induced Batf3-/- CD8α+ DCs. Furthermore, IL-12 treatment of Batf3-/- mice restored their capacity for in vivo cross-presentation of necrotic cell-associated antigens. Finally, the restored CD8α+ DCs primed CD8+ T cells against T. gondii-derived antigen, and produced IL-12 in vivo in response to T. gondii infection. Thus, IL-12 can induce development of CD8α+ DCs through a Batf3-independent mechanism, and these cells can function to both prime T cells as well as produce IL-12 during infection in vivo.

"]},{"key":"dc:title","label":"Title","values":["Batf3-Deficient Mice: Susceptibility to Toxoplasma gondii and Responses to IL-12 Treatment in vivo"]}]}],"canonical_facts":{"dc:contributor":["Kenneth M Murphy"],"dc:creator":["Mashayekhi, Mona"],"dc:date.available":["2013-08-26T07:00:00Z"],"dc:description.abstract":["

CD8α+ dendritic cells are important in vivo for cross-presentation of antigens derived from intracellular pathogens and tumors. Additionally, stimulation of IL-12 production by CD8α+ DCs has suggested a role for these cells in response to Toxoplasma gondii antigens, although no experiments have yet shown an in vivo requirement for these cells against T. gondii infection. Towards this goal, we examined T. gondii infection of Batf3-/- mice, which selectively lack only lymphoid-resident CD8α+ DCs and related peripheral CD103+ DCs. Batf3-/- mice were extremely susceptible to T. gondii infection, with defective priming of CD8+ T cells, and decreased production of IL-12 and IFNγ. IL-12 administration restored resistance in Batf3-/- mice, and mice in which IL-12 production was ablated only from CD8α+ DCs failed to control infection. These results reveal that the function of CD8α+ DCs extends beyond a role in cross-presentation and includes a critical role for activation of innate immunity through IL-12 production during T. gondii infection.

While investigating the immune responses of Batf3-/- mice to T. gondii infection, we made the surprising discovery that IL-12 treatment of infected Batf3-/- mice resulted in re-appearance of the CD8α+ DC population in the spleen. In addition, we show that IL-12-treatment alone in the absence of infection restored the CD8α+ DC population in Batf3-/- mice. Analysis of the restored cells by microarray revealed very few differences in gene expression between wild-type and IL-12-induced Batf3-/- CD8α+ DCs. Furthermore, IL-12 treatment of Batf3-/- mice restored their capacity for in vivo cross-presentation of necrotic cell-associated antigens. Finally, the restored CD8α+ DCs primed CD8+ T cells against T. gondii-derived antigen, and produced IL-12 in vivo in response to T. gondii infection. Thus, IL-12 can induce development of CD8α+ DCs through a Batf3-independent mechanism, and these cells can function to both prime T cells as well as produce IL-12 during infection in vivo.

"],"dc:identifier":["https://openscholarship.wustl.edu/etd/1054"],"dc:identifier.doi":["https://doi.org/10.7936/K7RJ4GG5"],"dc:language":["English (en)"],"dc:subject":["Batf3","CD8-alpha+ dendritic cells","IL-12","Toxoplasma gondii","Immunology and Infectious Disease"],"dc:title":["Batf3-Deficient Mice: Susceptibility to Toxoplasma gondii and Responses to IL-12 Treatment in vivo"],"thesis:degree_discipline":["Biology and Biomedical Sciences: Immunology"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T06:13:31Z"}