Pathogen adaptations during host-pathogen co-evolution can cause the host balance between immunity and immunopathology to rapidly shift. However, little is known in natural disease systems about the immunological pathways optimised through the trade-off between immunity and self-damage. The evolutionary interaction between the conjunctival bacterial infection Mycoplasma gallisepticum (MG) and its avian host, the house finch (Haemorhous mexicanus), can provide insights into such adaptations in immune regulation. Here we use experimental infections to reveal immune variation in conjunctival tissue for house finches captured from four distinct populations differing in the length of their co-evolutionary histories with MG and their disease tolerance (defined as disease severity per pathogen load) in controlled infection studies. To differentiate contributions of host versus pathogen evolution, we compared house finch responses to one of two MG isolates: the original VA1994 isolate and a more evolutionarily derived one, VA2013. To identify differential gene expression involved in initiation of the immune response to MG, we performed 3'-end transcriptomic sequencing (QuantSeq) of samples from the infection site, conjunctiva, collected 3-days post-infection. In response to MG, we observed an increase in general pro-inflammatory signalling, as well as T-cell activation and IL17 pathway differentiation, associated with a decrease in the IL12/IL23 pathway signalling. The immune response was stronger in response to the evolutionarily derived MG isolate compared to the original one, consistent with known increases in MG virulence over time. The host populations differed namely in pre-activation immune gene expression, suggesting population-specific adaptations. Compared to other populations, finches from Virginia, which have the longest co-evolutionary history with MG, showed significantly higher expression of anti-inflammatory genes and Th1 mediators. This may explain the evolution of disease tolerance to MG infection in VA birds. We also show a potential modulating role of BCL10, a positive B- and T-cell regulator activating the NFKB signalling. Our results illuminate potential mechanisms of house finch adaptation to MG-induced immunopathology, contributing to understanding of the host evolutionary responses to pathogen-driven shifts in immunity-immunopathology trade-offs.

• Klíčová slova
• adaptations diversifying populations, coevolution, emerging disease, host-pathogen interaction, inflammatory immune response, parasite, resistance, tolerance to infection,
• MeSH
• imunita MeSH
• konjunktiva MeSH
• mykoplazmové infekce * veterinární   mikrobiologie   MeSH
• pěnkavovití * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

Cytokinins are adenine and non-adenine derived heterogeneous class of regulatory molecules that participate in almost every aspect of plant biology. They also affect plant defense responses as well as help microbial pathogens to establish pathogenesis. The functional approaches that ensure desired and subtle modulations in the levels of plant cytokinins are highly instrumental in assessing their functions in plant immunity. Here, we describe a detailed working protocol regarding the enhanced production of cytokinins from plants that harbor isopentenyltransferase (IPT) enzyme gene under the control of 4xJERE (jasmonic acid and elicitor-responsive element) pathogen-inducible promoter. Our devised expression system is a context-dependent solution when it comes to investigating host-pathogen interactions under the modulated conditions of plant cytokinins.

• Klíčová slova
• Cytokinins, Host-pathogen interaction, Pathogen-inducible promoter, Transient plant transformation,
• MeSH
• cytokininy metabolismus   MeSH
• fenotyp MeSH
• geneticky modifikované rostliny MeSH
• imunita rostlin MeSH
• interakce hostitele a patogenu * imunologie   MeSH
• nemoci rostlin genetika   imunologie   mikrobiologie   MeSH
• regulace genové exprese u rostlin MeSH
• regulátory růstu rostlin metabolismus   MeSH
• signální transdukce MeSH
• transformace genetická MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• cytokininy MeSH
• regulátory růstu rostlin MeSH

Bacteria that are highly virulent, expressing high infectivity, and able to survive nebulization, pose great risk to the human population. One of these is Francisella tularensis, the etiological agent of tularemia. F. tularensis is a subject of intense scientific interest due to the fact that vaccines for its immunoprophylaxis in humans are not yet routinely available. One of the substantial obstacles in developing such vaccines is our insufficient knowledge of processes that initiate and regulate the expression of effective protective immunity against intracellular bacteria. Here, we present data documenting the different pattern of cellular behavior occurring in an environment unaffected by microbiota using the model of germ-free mice mono-associated with F. tularensis subsp. holarctica strain LVS in comparison with a classic specific-pathogen-free murine model during early stages of infection.

• Klíčová slova
• Cellular response, Francisella tularensis, Germ-free, Gnotobiont, Innate immunity,
• MeSH
• bakteriální vakcíny imunologie   MeSH
• cytokiny metabolismus   MeSH
• Francisella tularensis imunologie   patogenita   MeSH
• gnotobiologické modely imunologie   MeSH
• interakce hostitele a patogenu imunologie   MeSH
• mikrobiota MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední BALB C MeSH
• myši MeSH
• organismy bez specifických patogenů imunologie   MeSH
• peritoneum mikrobiologie   patologie   MeSH
• přirozená imunita MeSH
• slezina mikrobiologie   patologie   MeSH
• tularemie imunologie   mikrobiologie   patologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• bakteriální vakcíny MeSH
• cytokiny MeSH

Phagocytosis by hemocytes, Drosophila macrophages, is essential for resistance to Streptococcus pneumoniae in adult flies. Activated macrophages require an increased supply of energy and we show here that a systemic metabolic switch, involving the release of glucose from glycogen, is required for effective resistance to S. pneumoniae. This metabolic switch is mediated by extracellular adenosine, as evidenced by the fact that blocking adenosine signaling in the adoR mutant suppresses the systemic metabolic switch and decreases resistance to infection, while enhancing adenosine effects by lowering adenosine deaminase ADGF-A increases resistance to S. pneumoniae. Further, that ADGF-A is later expressed by immune cells during infection to regulate these effects of adenosine on the systemic metabolism and immune response. Such regulation proved to be important during chronic infection caused by Listeria monocytogenes. Lowering ADGF-A specifically in immune cells prolonged the systemic metabolic effects, leading to lower glycogen stores, and increased the intracellular load of L. monocytogenes, possibly by feeding the bacteria. An adenosine-mediated systemic metabolic switch is thus essential for effective resistance but must be regulated by ADGF-A expression from immune cells to prevent the loss of energy reserves and possibly to avoid the exploitation of energy by the pathogen.

• MeSH
• adenosin farmakologie   MeSH
• Drosophila melanogaster růst a vývoj   imunologie   metabolismus   mikrobiologie   MeSH
• energetický metabolismus MeSH
• extracelulární prostor metabolismus   MeSH
• fagocytóza účinky léků   imunologie   MeSH
• hemocyty účinky léků   imunologie   metabolismus   MeSH
• interakce hostitele a patogenu účinky léků   MeSH
• Listeria monocytogenes účinky léků   imunologie   metabolismus   MeSH
• listeriové infekce imunologie   metabolismus   mikrobiologie   MeSH
• makrofágy účinky léků   imunologie   metabolismus   MeSH
• mutace MeSH
• pneumokokové infekce imunologie   metabolismus   mikrobiologie   MeSH
• proteiny Drosophily genetika   metabolismus   MeSH
• signální transdukce účinky léků   imunologie   MeSH
• Streptococcus pneumoniae účinky léků   imunologie   metabolismus   MeSH
• vazodilatancia farmakologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adenosin MeSH
• adenosine deaminase-related growth factor, Drosophila MeSH Prohlížeč
• proteiny Drosophily MeSH
• vazodilatancia MeSH

Understanding how context (e.g., host species, environmental conditions) drives disease susceptibility is an essential goal of disease ecology. We hypothesized that in bat white-nose syndrome (WNS), species-specific host-pathogen interactions may partly explain varying disease outcomes among host species. We characterized bat and pathogen transcriptomes in paired samples of lesion-positive and lesion-negative wing tissue from bats infected with Pseudogymnoascus destructans in three parallel experiments. The first two experiments analyzed samples collected from the susceptible Nearctic Myotis lucifugus and the less-susceptible Nearctic Eptesicus fuscus, following experimental infection and hibernation in captivity under controlled conditions. The third experiment applied the same analyses to paired samples from infected, free-ranging Myotis myotis, a less susceptible, Palearctic species, following natural infection and hibernation (n = 8 sample pairs/species). Gene expression by P. destructans was similar among the three host species despite varying environmental conditions among the three experiments and was similar within each host species between saprophytic contexts (superficial growth on wings) and pathogenic contexts (growth in lesions on the same wings). In contrast, we observed qualitative variation in host response: M. lucifugus and M. myotis exhibited systemic responses to infection, while E. fuscus up-regulated a remarkably localized response. Our results suggest potential phylogenetic determinants of response to WNS and can inform further studies of context-dependent host-pathogen interactions.

• Klíčová slova
• Eptesicus fuscus, Myotis lucifugus, Myotis myotis, Pseudogymnoascus destructans, Disease ecology, emerging infectious diseases, host–pathogen interactions, susceptibility, virulence,
• MeSH
• Ascomycota genetika   patogenita   MeSH
• Chiroptera klasifikace   mikrobiologie   MeSH
• dermatomykózy mikrobiologie   veterinární   MeSH
• druhová specificita MeSH
• fylogeneze MeSH
• interakce hostitele a patogenu genetika   MeSH
• křídla zvířecí mikrobiologie   patologie   MeSH
• nos mikrobiologie   patologie   MeSH
• stanovení celkové genové exprese * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Disease can act as a driving force in shaping genetic makeup across populations, even species, if the impacts influence a particularly sensitive part of their life cycles. White-nose disease is caused by a fungal pathogen infecting bats during hibernation. The mycosis has caused massive population declines of susceptible species in North America, particularly in the genus Myotis. However, Myotis bats appear to tolerate infection in Eurasia, where the fungal pathogen has co-evolved with its bat hosts for an extended period of time. Therefore, with susceptible and tolerant populations, the fungal disease provides a unique opportunity to tease apart factors contributing to tolerance at a genomic level to and gain an understanding of the evolution of non-harmful in host-parasite interactions. To investigate if the fungal disease has caused adaptation on a genomic level in Eurasian bat species, we adopted both whole-genome sequencing approaches and a literature search to compile a set of 300 genes from which to investigate signals of positive selection in genomes of 11 Eurasian bats at the codon-level. Our results indicate significant positive selection in 38 genes, many of which have a marked role in responses to infection. Our findings suggest that white-nose syndrome may have applied a significant selective pressure on Eurasian Myotis-bats in the past, which can contribute their survival in co-existence with the pathogen. Our findings provide an insight on the selective pressure pathogens afflict on their hosts using methodology that can be adapted to other host-pathogen study systems.

• Klíčová slova
• Adaptation, Bats, Disease, Fungal pathogen, Positive selection, Tolerance,
• MeSH
• Chiroptera * mikrobiologie   genetika   MeSH
• genom MeSH
• genomika metody   MeSH
• interakce hostitele a patogenu genetika   MeSH
• molekulární evoluce MeSH
• mykózy mikrobiologie   veterinární   MeSH
• sekvenování celého genomu MeSH
• selekce (genetika) * MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Mammalian lungs are organs exhibiting the cellular and spatial complexity required for gas exchange to support life. The respiratory epithelium internally lining the airways is susceptible to infections due to constant exposure to inhaled microbes. Biomedical research into respiratory bacterial infections in humans has been mostly carried out using small mammalian animal models or two-dimensional, submerged cultures of undifferentiated epithelial cells. These experimental model systems have considerable limitations due to host specificity of bacterial pathogens and lack of cellular and morphological complexity. This review describes the in vitro differentiated and polarized airway epithelial cells of human origin that are used as a model to study respiratory bacterial infections. Overall, these models recapitulate key aspects of the complexity observed in vivo and can help in elucidating the molecular details of disease processes observed during respiratory bacterial infections.

• Klíčová slova
• Transwells, air-liquid interface, airway epithelium, bacterial pathogenesis, barrier function, host-pathogen interactions, innate immunity, in vitro models, polarized airway epithelial cells,
• MeSH
• Bacteria imunologie   MeSH
• bakteriální infekce imunologie   mikrobiologie   patologie   MeSH
• biologické modely * MeSH
• interakce hostitele a patogenu imunologie   MeSH
• lidé MeSH
• přirozená imunita imunologie   MeSH
• respirační sliznice imunologie   mikrobiologie   patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

HU protein is a member of nucleoid-associated proteins (NAPs) and is an important regulator of bacterial virulence, pathogenesis and survival. NAPs are mainly DNA structuring proteins that influence several molecular processes by binding the DNA. HU´s indispensable role in DNA-related processes in bacteria was described. HU protein is a necessary bacterial transcription factor and is considered to be a virulence determinant as well. Less is known about its direct role in host-pathogen interactions. The latest studies suggest that HU protein may be secreted outside bacteria and be a part of the extracellular matrix. Moreover, HU protein can be internalized in a host cell after bacterial infection. Its role in the host cell is not well described and further studies are extremely needed. Existing results suggest the involvement of HU protein in host cell immune response modulation in bacterial favor, which can help pathogens resist host defense mechanisms. A better understanding of the HU protein's role in the host cell will help to effective treatment development.

• Klíčová slova
• HU protein, bacterial secretion, histone-like protein, host-pathogen interaction, nucleoid-associated protein, virulence,
• MeSH
• bakteriální proteiny * genetika   MeSH
• DNA bakterií metabolismus   MeSH
• DNA vazebné proteiny * metabolismus   MeSH
• DNA chemie   MeSH
• faktory virulence MeSH
• interakce hostitele a patogenu MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• bakteriální proteiny * MeSH
• DNA bakterií MeSH
• DNA vazebné proteiny * MeSH
• DNA MeSH
• faktory virulence 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 imunologie   patogenita   MeSH
• brucelóza imunologie   MeSH
• cytoplazma mikrobiologie   MeSH
• dendritické buňky mikrobiologie   MeSH
• interakce hostitele a patogenu imunologie   MeSH
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

African populations remain underrepresented in studies of human genetic diversity, despite a growing interest in understanding how they have adapted to the diverse environments they live in. In particular, understanding the genetic basis of immune adaptation to pathogens is of paramount importance in a continent such as Africa, where the burden of infectious diseases is a major public health challenge. In this study, we investigated the molecular variation of four Human Leukocyte Antigens (HLA) class II genes (DRB1, DQA1, DQB1 and DPB1), directly involved in the immune response to parasitic infections, in more than 1000 individuals from 23 populations across North, East, Central and West Africa. By analyzing the HLA molecular diversity of these populations in relation to various geographical, cultural and environmental factors, we identified divergent genetic profiles for several (semi-)nomadic populations of the Sahel belt as a signature of their unique demography. In addition, we observed significant genetic structuring supporting both substantial geographic and linguistic differentiations within West Africa. Furthermore, neutrality tests suggest balancing selection has been shaping the diversity of these four HLA class II genes, which is consistent with molecular comparisons between HLA genes and their orthologs in chimpanzees (Patr). However, the most striking observation comes from linear modeling, demonstrating that the prevalence of Plasmodium falciparum, the primary pathogen of malaria in Africa, significantly explains a large proportion of the nucleotide diversity observed at the DPB1 gene. DPB1*01:01, a highly frequent allele in Burkinabé populations, is identified as a potential protective allele against malaria, suggesting that strong pathogen-driven positive selection at this gene has shaped HLA variation in Africa. Additionally, two low-frequency DRB1 alleles, DRB1*08:06 and DRB1*11:02, also show significant associations with P. falciparum prevalence, supporting resistance to malaria is determined by multigenic and/or multiallelic combinations rather than single allele effects.

• Klíčová slova
• Africa, HLA, human molecular diversity, malaria, pathogen‐driven selection, plasmodium falciparum,
• Publikační typ
• časopisecké články MeSH