Immune responses to intracellular pathogens depend largely upon the activation of T helper type 1-dependent mechanisms. The contribution of B cells to establishing protective immunity has long been underestimated. Francisella tularensis, including a number of subspecies, provides a suitable model for the study of immune responses against intracellular bacterial pathogens. We previously demonstrated that Francisella infects B cells and activates B-cell subtypes to produce a number of cytokines and express the activation markers. Recently, we documented the early production of natural antibodies as a consequence of Francisella infection in mice. Here, we summarize current knowledge on the innate and acquired humoral immune responses initiated by Francisella infection and their relationships with the immune defense systems.

• Keywords
• B cells, Francisella tularensis, intracellular pathogen, natural antibodies, natural immunity,
• Publication type
• Journal Article MeSH
• Review MeSH

There remains to this day a great gap in understanding as to the role of B cells and their products-antibodies and cytokines-in mediating the protective response to Francisella tularensis, a Gram-negative coccobacillus belonging to the group of facultative intracellular bacterial pathogens. We previously have demonstrated that Francisella interacts directly with peritoneal B-1a cells. Here, we demonstrate that, as early as 12 h postinfection, germ-free mice infected with Francisella tularensis produce infection-induced antibody clones reacting with Francisella tularensis proteins having orthologs or analogs in eukaryotic cells. Production of some individual clones was limited in time and was influenced by virulence of the Francisella strain used. The phylogenetically stabilized defense mechanism can utilize these early infection-induced antibodies both to recognize components of the invading pathogens and to eliminate molecular residues of infection-damaged self cells.

• MeSH
• B-Lymphocytes immunology   metabolism   MeSH
• Cytokines metabolism   MeSH
• Francisella tularensis pathogenicity   MeSH
• Disease Models, Animal MeSH
• Mice, Inbred BALB C MeSH
• Mice MeSH
• Tularemia immunology   microbiology   MeSH
• Antibody Formation MeSH
• Virulence MeSH
• Animals MeSH
• Check Tag
• Mice MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Cytokines MeSH

As dendritic cells (DCs) are among the first cells to encounter antigens, these cells trigger both innate and T cell responses, and are the most potent antigen-presenting cells. Brucella spp., which is an intracellular facultative and stealthy pathogen, is able to evade the bactericidal activities of professional phagocytes. Several studies have demonstrated that Brucella can survive and replicate intracellularly, thereby provoking impaired maturation of DCs. Therefore, the interaction between DCs and Brucella becomes an interesting model to study the immune response. In this review, we first will describe the most common techniques for DCs differentiation in vitro as well as general features of brucellosis. Then, the interaction of DCs and Brucella, including pathogen recognition, molecular mechanisms of bacterial pathogenesis, and intracellular trafficking of Brucella to subvert innate response, will be reviewed. Finally, we will debate diversity in immunological DC response and the controversial role of DC activation against Brucella infection.

• MeSH
• Brucella immunology   pathogenicity   MeSH
• Brucellosis immunology   MeSH
• Cytoplasm microbiology   MeSH
• Dendritic Cells microbiology   MeSH
• Host-Pathogen Interactions immunology   MeSH
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Check Tag
• Humans MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Dendritic cells (DCs) infected by Francisella tularensis are poorly activated and do not undergo classical maturation process. Although reasons of such unresponsiveness are not fully understood, their impact on the priming of immunity is well appreciated. Previous attempts to explain the behavior of Francisella-infected DCs were hypothesis-driven and focused on events at later stages of infection. Here, we took an alternative unbiased approach by applying methods of global phosphoproteomics to analyze the dynamics of cell signaling in primary DCs during the first hour of infection by Francisella tularensis Presented results show that the early response of DCs to Francisella occurs in phases and that ERK and p38 signaling modules induced at the later stage are differentially regulated by virulent and attenuated ΔdsbA strain. These findings imply that the temporal orchestration of host proinflammatory pathways represents the integral part of Francisella life-cycle inside hijacked DCs.

• MeSH
• Cell Line MeSH
• Dendritic Cells metabolism   microbiology   MeSH
• Extracellular Signal-Regulated MAP Kinases metabolism   MeSH
• Phosphorylation MeSH
• Francisella tularensis * MeSH
• p38 Mitogen-Activated Protein Kinases metabolism   MeSH
• Mice, Inbred C57BL MeSH
• Tularemia metabolism   MeSH
• Animals MeSH
• Check Tag
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Names of Substances
• Extracellular Signal-Regulated MAP Kinases MeSH
• p38 Mitogen-Activated Protein Kinases MeSH