Many pathogens have evolved sophisticated strategies to evade autophagy, a crucial cellular defense mechanism that typically targets and degrades invading microorganisms. By subverting or inhibiting autophagy, these pathogens can create a more favorable environment for their replication and survival within the host. For instance, some bacteria secrete factors that block autophagosome formation, while others might escape from autophagosomes before degradation. These evasion tactics are critical for the pathogens' ability to establish and maintain infections. Understanding the mechanisms by which pathogens avoid autophagy is crucial for developing new therapeutic strategies, as enhancing autophagy could bolster the host's immune response and aid in the elimination of pathogenic bacteria. Francisella tularensis can manipulate host cell pathways to prevent its detection and destruction by autophagy, thereby enhancing its virulence. Given the potential for F. tularensis to be used as a bioterrorism agent due to its high infectivity and ability to cause severe disease, research into how this pathogen evades autophagy is of critical importance. By unraveling these mechanisms, new therapeutic approaches could be developed to enhance autophagic responses and strengthen host defense against this and other similarly evasive pathogens.

• Klíčová slova
• Francisella, autophagy, bacterial pathogenesis, host-pathogen interaction, virulence,
• MeSH
• autofagie * MeSH
• faktory virulence metabolismus   MeSH
• Francisella tularensis * patogenita   imunologie   fyziologie   MeSH
• imunitní únik * MeSH
• interakce hostitele a patogenu * MeSH
• lidé MeSH
• tularemie mikrobiologie   imunologie   MeSH
• virulence MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• faktory virulence MeSH

Primary interaction of an intracellular bacterium with its host cell is initiated by activation of multiple signaling pathways in response to bacterium recognition itself or as cellular responses to stress induced by the bacterium. The leading molecules in these processes are cell surface membrane receptors as well as cytosolic pattern recognition receptors recognizing pathogen-associated molecular patterns or damage-associated molecular patterns induced by the invading bacterium. In this review, we demonstrate possible sequences of events leading to recognition of Francisella tularensis, present findings on known mechanisms for manipulating cell responses to protect Francisella from being killed, and discuss newly published data from the perspective of early stages of host-pathogen interaction.

• Klíčová slova
• Francisella tularensis, innate immune recognition, intracellular replication, phagocytosis, signaling pathways,
• MeSH
• alarminy genetika   imunologie   MeSH
• bakteriální proteiny genetika   imunologie   MeSH
• fagocytóza genetika   MeSH
• Francisella tularensis genetika   imunologie   patogenita   MeSH
• interakce hostitele a patogenu genetika   imunologie   MeSH
• lidé MeSH
• makrofágy imunologie   mikrobiologie   MeSH
• PAMP struktury imunologie   metabolismus   MeSH
• přirozená imunita * MeSH
• receptory buněčného povrchu genetika   imunologie   MeSH
• receptory rozpoznávající vzory genetika   imunologie   MeSH
• regulace genové exprese MeSH
• signální transdukce MeSH
• tularemie genetika   imunologie   mikrobiologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• alarminy MeSH
• bakteriální proteiny MeSH
• PAMP struktury MeSH
• receptory buněčného povrchu MeSH
• receptory rozpoznávající vzory 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
• buněčné linie MeSH
• dendritické buňky metabolismus   mikrobiologie   MeSH
• extracelulárním signálem regulované MAP kinasy metabolismus   MeSH
• fosforylace MeSH
• Francisella tularensis * MeSH
• mitogenem aktivované proteinkinasy p38 metabolismus   MeSH
• myši inbrední C57BL MeSH
• tularemie metabolismus   MeSH
• zvířata MeSH
• Check Tag
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• extracelulárním signálem regulované MAP kinasy MeSH
• mitogenem aktivované proteinkinasy p38 MeSH