Rickettsial agents are sensed by pattern recognition receptors but lack pathogen-associated molecular patterns commonly observed in facultative intracellular bacteria. Due to these molecular features, the order Rickettsiales can be used to uncover broader principles of bacterial immunity. Here, we used the bacterium Anaplasma phagocytophilum, the agent of human granulocytic anaplasmosis, to reveal a novel microbial surveillance system. Mechanistically, we discovered that upon A. phagocytophilum infection, cytosolic phospholipase A2 cleaves arachidonic acid from phospholipids, which is converted to the eicosanoid prostaglandin E2 (PGE2) via cyclooxygenase 2 (COX2) and the membrane associated prostaglandin E synthase-1 (mPGES-1). PGE2-EP3 receptor signaling leads to activation of the NLRC4 inflammasome and secretion of interleukin (IL)-1β and IL-18. Importantly, the receptor-interacting serine/threonine-protein kinase 2 (RIPK2) was identified as a major regulator of the immune response against A. phagocytophilum. Accordingly, mice lacking COX2 were more susceptible to A. phagocytophilum, had a defect in IL-18 secretion and exhibited splenomegaly and damage to the splenic architecture. Remarkably, Salmonella-induced NLRC4 inflammasome activation was not affected by either chemical inhibition or genetic ablation of genes associated with PGE2 biosynthesis and signaling. This divergence in immune circuitry was due to reduced levels of the PGE2-EP3 receptor during Salmonella infection when compared to A. phagocytophilum. Collectively, we reveal the existence of a functionally distinct NLRC4 inflammasome illustrated by the rickettsial agent A. phagocytophilum.

• MeSH
• Anaplasma phagocytophilum imunologie   MeSH
• dinoproston imunologie   MeSH
• ehrlichióza imunologie   MeSH
• ELISA MeSH
• imunoblotting MeSH
• inflamasomy imunologie   MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• myši knockoutované MeSH
• myši MeSH
• proteiny regulující apoptózu imunologie   MeSH
• proteiny vázající vápník imunologie   MeSH
• receptory prostaglandinů E - podtyp EP3 imunologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Tick saliva contains a number of effector molecules that inhibit host immunity and facilitate pathogen transmission. How tick proteins regulate immune signaling, however, is incompletely understood. Here, we describe that loop 2 of sialostatin L2, an anti-inflammatory tick protein, binds to annexin A2 and impairs the formation of the NLRC4 inflammasome during infection with the rickettsial agent Anaplasma phagocytophilum Macrophages deficient in annexin A2 secreted significantly smaller amounts of interleukin-1β (IL-1β) and IL-18 and had a defect in NLRC4 inflammasome oligomerization and caspase-1 activation. Accordingly, Annexin a2-deficient mice were more susceptible to A. phagocytophilum infection and showed splenomegaly, thrombocytopenia, and monocytopenia. Providing translational support to our findings, better binding of annexin A2 to sialostatin L2 in sera from 21 out of 23 infected patients than in sera from control individuals was also demonstrated. Overall, we establish a unique mode of inflammasome evasion by a pathogen, centered on a blood-feeding arthropod.

• MeSH
• Anaplasma phagocytophilum genetika   imunologie   MeSH
• annexin A2 chemie   genetika   imunologie   MeSH
• arachnida jako vektory chemie   genetika   imunologie   MeSH
• cystatiny chemie   genetika   imunologie   MeSH
• ehrlichióza imunologie   mikrobiologie   patologie   MeSH
• Escherichia coli genetika   metabolismus   MeSH
• imunitní únik * MeSH
• inflamasomy genetika   imunologie   MeSH
• interleukin-18 genetika   imunologie   MeSH
• interleukin-1beta genetika   imunologie   MeSH
• kaspasa 1 genetika   imunologie   MeSH
• kaspasy genetika   imunologie   MeSH
• klíště chemie   genetika   imunologie   MeSH
• lidé MeSH
• makrofágy imunologie   mikrobiologie   MeSH
• molekulární modely MeSH
• myši MeSH
• protein - isoformy chemie   genetika   imunologie   MeSH
• proteiny regulující apoptózu chemie   genetika   imunologie   MeSH
• proteiny vázající vápník chemie   genetika   imunologie   MeSH
• regulace genové exprese MeSH
• rekombinantní proteiny chemie   genetika   imunologie   MeSH
• sekvence aminokyselin MeSH
• signální transdukce MeSH
• vazba proteinů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Grasses belong to major sources of inhaled allergens. The knowledge of particular molecules responsible for hypersensitivity is of crucial importance for better understanding of individual differences among single allergic subjects and allergic populations living in various world-areas. METHODS: Specific-IgE-antibodies against Phl p 1, Phl p 5, Phl p 7, Phl p 12 were detected in a group of 130 Phleum-allergic-subjects (82 children, 48 adults). RESULTS: Phl p 1 antibodies were detected in most pediatric and adult patients, however, the children were associated with higher RAST classes more often. Anti-Phl p 5-antibodies were found more frequently in adults. An increase was observed in the number of pediatric patients reacting to Phl p 7 and Phl p 12. There were no differences in concentrations of specific-IgE against Phl p 5, Phl p 7 and Phl p 12 depending on age. Almost 10% of allergic children produced antibodies directed exclusively against minor allergens or did not produce specific-IgE-antibodies against tested molecules. Part of the patients reacted to profilin and calcium-binding protein originating from only one source (Phl p 12/Bet v 2 and Phl p 7/Bet v 4). CONCLUSIONS: Antibodies against Phl p 1 and Phl p 5 can be used as a marker of allergy to grasses in adult patients. Children reacted exclusively to minor allergens more frequently than adults. Prolonged allergen exposure is evidently necessary to induce sensitization to Phl p 5. A high level of homology between profilins and calcium-binding proteins enables only one allergen to be used for diagnostic purposes but a possibility of a reaction to species-bound epitopes should be taken into account.

• MeSH
• alergeny imunologie   MeSH
• antigeny rostlinné imunologie   MeSH
• biologické markery krev   MeSH
• dítě MeSH
• dospělí MeSH
• epitopy MeSH
• imunoglobulin E krev   MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• Phleum imunologie   MeSH
• předškolní dítě MeSH
• profiliny imunologie   MeSH
• proteiny vázající vápník imunologie   MeSH
• pyl škodlivé účinky   imunologie   MeSH
• rostlinné proteiny imunologie   MeSH
• senioři MeSH
• sezónní alergická rýma krev   diagnóza   imunologie   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND: Birch pollen belongs to the major allergen triggers in the spring season in Europe. Our rapidly expanding knowledge of the allergenic molecules enables us to better recognize the individual differences between the reactivity of specific IgE antibodies of individual patients and allergic populations living in various regions of the world. METHOD: In a group of birch pollen-allergic patients living in the Czech Republic (107 children, 71 adults) we detected the presence of Bet v1, Bet v2 and Bet v4 specific IgE antibodies. RESULTS: Bet v1 specific IgE antibodies were identified in most patients without any significant differences between children and adults. Bet v2 positivity was found more frequently in the group of children than in adults (p = 0.02). In most adult patients Bet v1 monospecificity was more expressed as compared to the pediatric group. More allergic subjects reacted against minor birch allergens in the pediatric group (p = 0.02). Specific IgE antibodies against Bet v1 were not detected in 10% of the tested patients. In this group, 5% of birch pollen-allergic patients were found to not have specific IgE antibodies against any of the tested recombinant allergens. CONCLUSION: The investigation of specific IgE antibodies against Bet v1, Bet v2 and Bet v4 demonstrated that the specificity of allergen-induced IgE antibodies in birch pollen-allergic individuals is dependent not only on the region in which a patient lives but also on age. Especially in children, there is an increase in the number of allergic subjects who do not react exclusively against the major allergen. The question is whether some allergen-specific IgE antibodies will disappear depending on age or on the contrary whether their synthesis will be increased.

• MeSH
• alergie imunologie   MeSH
• antigeny rostlinné imunologie   MeSH
• bříza imunologie   MeSH
• dítě MeSH
• dospělí MeSH
• imunoglobulin E krev   imunologie   MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• předškolní dítě MeSH
• proteiny vázající vápník imunologie   MeSH
• pyl imunologie   MeSH
• rostlinné proteiny imunologie   MeSH
• senioři MeSH
• věkové faktory MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• MeSH
• biologické markery analýza   MeSH
• finanční podpora výzkumu jako téma MeSH
• lidé MeSH
• monocyty imunologie   MeSH
• neutrofily imunologie   MeSH
• proteiny vázající vápník fyziologie   chemie   imunologie   MeSH
• zánět metabolismus   MeSH
• zinek metabolismus   MeSH
• Check Tag
• lidé MeSH

• MeSH
• finanční podpora výzkumu jako téma MeSH
• fluorescenční mikroskopie využití   MeSH
• histocytochemie metody   MeSH
• imunoelektronová mikroskopie využití   MeSH
• krysa rodu rattus MeSH
• proteiny vázající vápník fyziologie   imunologie   MeSH
• srdce anatomie a histologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH

• MeSH
• autoimunitní nemoci imunologie   MeSH
• autoprotilátky krev   MeSH
• dítě MeSH
• dospělí MeSH
• imunoglobulin A krev   MeSH
• imunoglobulin G krev   MeSH
• lidé MeSH
• proteiny vázající vápník imunologie   MeSH
• ribonukleoproteiny imunologie   MeSH
• senioři MeSH
• western blotting MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• lidé MeSH
• senioři MeSH

• MeSH
• celiakie imunologie   krev   MeSH
• dítě MeSH
• dospělí MeSH
• gliadin imunologie   MeSH
• imunoglobulin A krev   MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• proteiny vázající vápník imunologie   MeSH
• protilátky krev   MeSH
• senioři MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• senioři MeSH
• ženské pohlaví MeSH

• MeSH
• proteiny vázající vápník imunologie   metabolismus   MeSH
• receptory imunologické MeSH
• reperfuzní poškození MeSH
• tranzitorní ischemická ataka MeSH

• MeSH
• autoantigeny imunologie   MeSH
• celiakie imunologie   MeSH
• gliadin imunologie   MeSH
• imunoglobulin A imunologie   MeSH
• krysa rodu rattus MeSH
• lidé MeSH
• proteiny vázající vápník imunologie   MeSH
• ribonukleoproteiny imunologie   MeSH
• sekvence aminokyselin MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• lidé MeSH
• zvířata MeSH
• Publikační typ
• srovnávací studie MeSH