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.

• Klíčová slova
• B cells, Francisella tularensis, intracellular pathogen, natural antibodies, natural immunity,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

SARS-CoV-2 infection induces the production of autoantibodies, which is significantly associated with complications during hospitalization and a more severe prognosis in COVID-19 patients. Such a response of the patient's immune system may reflect (1) the dysregulation of the immune response or (2) it may be an attempt to regulate itself in situations where the non-infectious self poses a greater threat than the infectious non-self. Of significance may be the primary virus-host cell interaction where the surface-bound ACE2 ectoenzyme plays a critical role. Here, we present a brief analysis of recent findings concerning the immune recognition of SARS-CoV-2, which, we believe, favors the second possibility as the underlying reason for the production of autoantibodies during COVID-19.

• Klíčová slova
• ACE2 signaling, COVID-19, SARS-CoV-2, autoantibodies, innate immune recognition,
• Publikační typ
• časopisecké články 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-lymfocyty imunologie   metabolismus   MeSH
• cytokiny metabolismus   MeSH
• Francisella tularensis patogenita   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• tularemie imunologie   mikrobiologie   MeSH
• tvorba protilátek MeSH
• virulence MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytokiny 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

The intracellular bacterial pathogen Francisella tularensis causes serious infectious disease in humans and animals. Moreover, F. tularensis, a highly infectious pathogen, poses a major concern for the public as a bacterium classified under Category A of bioterrorism agents. Unfortunately, research has so far failed to develop effective vaccines, due in part to the fact that the pathogenesis of intracellular bacteria is not fully understood and in part to gaps in our understanding of innate immune recognition processes leading to the induction of adaptive immune response. Recent evidence supports the concept that immune response to external stimuli in the form of bacteria is guided by the primary interaction of the bacterium with the host cell. Based on data from different Francisella models, we present here the basic paradigms of the emerging innate immune recognition concept. According to this concept, the type of cell and its receptor(s) that initially interact with the target constitute the first signaling window; the signals produced in the course of primary interaction of the target with a reacting cell act in a paracrine manner; and the innate immune recognition process as a whole consists in a series of signaling windows modulating adaptive immune response. Finally, the host, in the strict sense, is the interacting cell.

• Klíčová slova
• Francisella tularensis, immune recognition, innate immunity, intracellular bacteria, signaling windows concept, spatiotemporal network,
• MeSH
• adaptivní imunita MeSH
• Francisella tularensis imunologie   MeSH
• imunitní systém MeSH
• interakce hostitele a patogenu imunologie   MeSH
• lidé MeSH
• modely nemocí na zvířatech MeSH
• myši MeSH
• parakrinní signalizace imunologie   MeSH
• přirozená imunita * MeSH
• tularemie imunologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH