Immunity to Francisella

Center for Biologics Evaluation and Research, U.S. Food and Drug Administration Bethesda, MD, USA.
Frontiers in Microbiology (Impact Factor: 3.99). 02/2011; 2:26. DOI: 10.3389/fmicb.2011.00026
Source: PubMed


In recent years, studies on the intracellular pathogen Francisella tularensis have greatly intensified, generating a wealth of new information on the interaction of this organism with the immune system. Here we review the basic elements of the innate and adaptive immune responses that contribute to protective immunity against Francisella species, with special emphasis on new data that has emerged in the last 5 years. Most studies have utilized the mouse model of infection, although there has been an expansion of work on human cells and other new animal models. In mice, basic immune parameters that operate in defense against other intracellular pathogen infections, such as interferon gamma, TNF-α, and reactive nitrogen intermediates, are central for control of Francisella infection. However, new important immune mediators have been revealed, including IL-17A, Toll-like receptor 2, and the inflammasome. Further, a variety of cell types in addition to macrophages are now recognized to support Francisella growth, including epithelial cells and dendritic cells. CD4(+) and CD8(+) T cells are clearly important for control of primary infection and vaccine-induced protection, but new T cell subpopulations and the mechanisms employed by T cells are only beginning to be defined. A significant role for B cells and specific antibodies has been established, although their contribution varies greatly between bacterial strains of lower and higher virulence. Overall, recent data profile a pathogen that is adept at subverting host immune responses, but susceptible to many elements of the immune system's antimicrobial arsenal.

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Available from: Siobhán C Cowley,
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    • "Fish & Shellfish Immunology vaccination with killed bacteria induces an antibody response with only limited protection [16]. Production of membrane vesicles by cells is a conserved mechanism occurring throughout all domains of life [17]. "
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    ABSTRACT: Infection of fish with the facultative intracellular bacterium Francisella noatunensis remains an unresolved problem for aquaculture industry worldwide as it is difficult to vaccinate against without using live attenuated vaccines. Outer membrane vesicles (OMVs) are biological structures shed by Gramnegative bacteria in response to various environmental stimuli. OMVs have successfully been used to vaccinate against both intracellular and extracellular pathogens, due to an ability to stimulate innate, cell-mediated and humoral immune responses. We show by using atomic force and electron microscopy that the fish pathogenic bacterium E noatunensis subspecies noatunensis (F.n.n.) shed OMVs both in vitro into culture medium and in vivo in a zebrafish infection model. The main protein constituents of the OMV are IgIC, PdpD and PdpA, all known Francisella virulence factors, in addition to the outer membrane protein FopA and the chaperonin GroEL, as analyzed by mass spectrometry. The vesicles, when used as a vaccine, reduced proliferation of the bacterium and protected zebrafish when subsequently challenged with a high dose of F.n.n. without causing adverse effects for the host. Also granulomatous responses were reduced in F.n.n.-challenged zebrafish after OMV vaccination. Taken together, the data support the possible use of OMVs as vaccines against francisellosis in fish. (C) 2014 The Authors. Published by Elsevier Ltd.
    Fish &amp Shellfish Immunology 10/2014; 42(1). DOI:10.1016/j.fsi.2014.10.025 · 2.67 Impact Factor
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    • "The results of studies on immune response to Francisella e mainly conducted on the murine model utilizing live vaccine strain e have documented a significant role for B cells in controlling F. tularensis infection. It is generally accepted that B cell impact on the protection against Francisella infection mainly varies between bacterial strains of lower and higher virulence [6] [7]. A recent study, directed to defining the requirements for protection against virulent F. tularensis and utilizing a convalescent murine model of infection, demonstrated, however, that abTCR-positive cells, gdTCR-positive cells, as well as B cells are necessary in order to survive primary SchuS4 infection [8]. "
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    ABSTRACT: Francisella tularensis, a facultative intracellular Gram-negative bacterium, causes the illness tularemia. The infection of mice with live vaccine strain is considered to be a model of human tularemia. F. tularensis infects predominantly such phagocytic cells as macrophages or neutrophils, but it also infects non-phagocytic hepatocytes, epithelial cells, and murine and human B cell lines. Based on work with the murine tularemia model, we report here that F. tularensis LVS infects peritoneal CD19+ cells – exclusively B-1a cells – early after intraperitoneal infection in vivo. The peritoneal and consequently spleen CD19+ cells are activated by the F. tularensis LVS infection to express the activation markers from MHC class II, CD25, CD54, CD69, and the co-stimulatory molecules CD80 and CD86. As early as 12 h post-infection, the peritoneal CD19+ cells produce IFN-γ, IL-1β, IL-4, IL-6, IL-12, IL-17, IL-23, and TNF-α. The spleen CD19+ cells respond to infection with some delay. Moreover, the F. tularensis infected A20 B cell line activates CD3+ spleen cells isolated from naïve mice. Thus, the data presented here suggest that B cells have all the attributes to actively participate in the induction and regulation of the adaptive immune response during early stages of F. tularensis infection.
    Microbial Pathogenesis 10/2014; 75. DOI:10.1016/j.micpath.2014.08.009 · 1.79 Impact Factor
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    • "Mice infected with a sublethal infectious dose generate a robust antibody response characterized by specific IgG2 and IgM.107 Rats generate a similar antibody profile against F. tularensis LVS.110 Although antibodies are induced against a variety of bacterial antigens, a large proportion of the humoral response is directed against LPS in both mice and humans.111–113 "
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    ABSTRACT: Francisella tularensis is an intracellular Gram-negative bacterium that causes life-threatening tularemia. Although the prevalence of natural infection is low, F. tularensis remains a tier I priority pathogen due to its extreme virulence and ease of aerosol dissemination. F. tularensis can infect a host through multiple routes, including the intradermal and respiratory routes. Respiratory infection can result from a very small inoculum (ten organisms or fewer) and is the most lethal form of infection. Following infection, F. tularensis employs strategies for immune evasion that delay the immune response, permitting systemic distribution and induction of sepsis. In this review we summarize the current knowledge of F. tularensis in an immunological context, with emphasis on the host response and bacterial evasion of that response.
    Infection and Drug Resistance 09/2014; 7:239-51. DOI:10.2147/IDR.S53700
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