Protective potential of outer membrane vesicles derived from a virulent strain of Francisella tularensis

Front Microbiol. 2024 Mar 12:15:1355872. doi: 10.3389/fmicb.2024.1355872. eCollection 2024.

Abstract

Francisella tularensis secretes tubular outer membrane vesicles (OMVs) that contain a number of immunoreactive proteins as well as virulence factors. We have reported previously that isolated Francisella OMVs enter macrophages, cumulate inside, and induce a strong pro-inflammatory response. In the current article, we present that OMVs treatment of macrophages also enhances phagocytosis of the bacteria and suppresses their intracellular replication. On the other hand, the subsequent infection with Francisella is able to revert to some extent the strong pro-inflammatory effect induced by OMVs in macrophages. Being derived from the bacterial surface, isolated OMVs may be considered a "non-viable mixture of Francisella antigens" and as such, they present a promising protective material. Immunization of mice with OMVs isolated from a virulent F. tularensis subsp. holarctica strain FSC200 prolonged the survival time but did not fully protect against the infection with a lethal dose of the parent strain. However, the sera of the immunized animals revealed unambiguous cytokine and antibody responses and proved to recognize a set of well-known Francisella immunoreactive proteins. For these reasons, Francisella OMVs present an interesting material for future protective studies.

Keywords: FSC200; Francisella tularensis; host-pathogen interaction; outer membrane vesicles; vaccination.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This work was supported by the Czech Science Foundation (project no. 17-04010S); and by the Ministry of Defence of the Czech Republic “Long Term Organization Development Plan 1011” – Healthcare Challenges of WMD II of the Military Faculty of Medicine Hradec Kralove, University of Defence, Czech Republic (project no: DZRO-FVZ22-ZHN II).