Presenting Author: Kelly N Deobald
, PhD Candidate at Washington State Univ. Col. of Vet. Med.
Abstract:
Merocytophagy is a specialized phagocytic process identified in macrophages characterized by the transfer of cell membrane and cytosolic content between donor and recipient populations. Transfer is enhanced when cells are infected with intracellular pathogens, including Francisella tularensis, and cells stimulated with PRR agonists similarly show enhanced merocytophagy. We hypothesize that merocytophagy acts as an immune surveillance mechanism and contributes to expansion of the immune response to infection. Antigen presenting cells, especially dendritic cells (DC), that acquire pathogen via merocytophagy may be able to present bacterial antigens to activate T cells, thereby contributing to the protective response to pathogens. Our data demonstrate that DC acquire intracellular content including F. tularensis bacteria as a consequence of merocytophagy in vitro. Preliminary data generated in an OVA model of antigen presentation suggest that DC cross-present merocytophagy-acquired antigen to activate CD8+ T cells. Finally, we found that mice vaccinated with a mutant strain of F. tularensis developed to model merocytophagy transfer were protected from lethal inoculation with the virulent strain with efficacy nearing that of mice vaccinated with wild-type strain. While more work is needed to fully elucidate the mechanism behind merocytophagy, our data support the hypothesis that merocytophagy functions as a protective immune surveillance mechanism in F. tularensis infection.
Dendritic cells present antigen acquired via merocytophagy as an immune surveillance mechanism
Category
Poster and Podium (Block Symposium)
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Date: May 4 Presentation Time: 11:30 AM to 12:45 PM Room: Exhibit Hall F1