RESUMEN
The development of safe subunit vaccines requires adjuvants that augment immunogenicity of non-replicating protein-based antigens. Current vaccines against infectious diseases preferentially induce protective antibodies driven by adjuvants such as alum. However, the contribution of antibody to host defense is limited for certain classes of infectious diseases such as fungi, whereas animal studies and clinical observations implicate cellular immunity as an essential component of the resolution of fungal pathogens. Here, we decipher the structural bases of a newly identified glycoprotein ligand of Dectin-2 with potent adjuvancy, Blastomyces endoglucanase-2 (Bl-Eng2). We also pinpoint the developmental steps of antigen-specific CD4+ and CD8+ T responses augmented by Bl-Eng2 including expansion, differentiation and tissue residency. Dectin-2 ligation led to successful systemic and mucosal vaccination against invasive fungal infection and Influenza A infection, respectively. O-linked glycans on Bl-Eng2 applied at the skin and respiratory mucosa greatly augment vaccine subunit- induced protective immunity against lethal influenza and fungal pulmonary challenge.
Asunto(s)
Anticuerpos Antivirales/inmunología , Blastomyces/inmunología , Vacunas Fúngicas/inmunología , Infecciones por Orthomyxoviridae/inmunología , Adyuvantes Inmunológicos , Animales , Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD8-positivos/inmunología , Celulasa/inmunología , Vacunas contra la Influenza/inmunologíaRESUMEN
How do novel fire regimes and a long history of fire suppression influence species genetic diversity? Genetic diversity provides the raw materials for sustaining viable populations and for allowing adaptation to novel environmental challenges, and at present, few studies address the genetic responses of animals to fire management. Here we study the genetic responses of 2 butterfly species to a landscape gradient of fire timing and severity in Yosemite National Park using a large set of genome-wide single nucleotide polymorphisms (SNPs). Butterflies are important bio-indicators of invertebrate diversity and play important roles in both bottom-up and top-down ecosystem processes, and typically increase in abundance following wildfires, due to an increase in abundance of flowering plants. However, it is not clear how genetic diversity and genetic connectivity of butterflies respond to landscape change following fire, and whether fire management has positive or negative effects. We found evidence to suggest that fire increases genetic diversity and reduces isolation in 2 butterfly species, but that aspects of the fire regime (severity, extent, timing, and frequency) differ in importance depending on the ecology of the specific species. This research is the first study to address fire management impacts on genetic diversity in invertebrates, and the results will allow fire managers to predict that fire reintroduction in protected areas will generally benefit butterfly populations.
Asunto(s)
Mariposas Diurnas , Incendios , Incendios Forestales , Animales , Mariposas Diurnas/genética , Ecosistema , Variación GenéticaRESUMEN
Novel transmission routes can directly impact the evolutionary ecology of infectious diseases, with potentially dramatic effect on host populations and knock-on effects on the wider host community. The invasion of Varroa destructor, an ectoparasitic viral vector in Western honeybees, provides a unique opportunity to examine how a novel vector affects disease epidemiology in a host community. This specialist honeybee mite vectors deformed wing virus (DWV), an important re-emerging honeybee pathogen that also infects wild bumblebees. Comparing island honeybee and wild bumblebee populations with and without V. destructor, we show that V. destructor drives DWV prevalence and titre in honeybees and sympatric bumblebees. Viral genotypes are shared across hosts, with the potentially more virulent DWV-B overtaking DWV-A in prevalence in a current epidemic. This demonstrates disease emergence across a host community driven by the acquisition of a specialist novel transmission route in one host, with dramatic community level knock-on effects.
Asunto(s)
Abejas , Varroidae , Animales , Abejas/parasitología , Vectores de Enfermedades , Dinámica Poblacional , Varroidae/patogenicidadRESUMEN
Emergent infectious diseases can have a devastating impact on host populations. The high selective pressures on both the hosts and the pathogens frequently lead to rapid adaptations not only in pathogen virulence but also host resistance following an initial outbreak. However, it is often unclear whether hosts will evolve to avoid infection-associated fitness costs by preventing the establishment of infection (here referred to as qualitative resistance) or by limiting its deleterious effects through immune functioning (here referred to as quantitative resistance). Equally, the evolutionary repercussions these different resistance mechanisms have for the pathogen are often unknown. Here, we investigate the co-evolutionary dynamics of pathogen virulence and host resistance following the epizootic outbreak of the highly pathogenic bacterium Mycoplasma gallisepticum in North American house finches (Haemorhous mexicanus). Using an evolutionary modelling approach and with a specific emphasis on the evolved resistance trait, we demonstrate that the rapid increase in the frequency of resistant birds following the outbreak is indicative of strong selection pressure to reduce infection-associated mortality. This, in turn, created the ecological conditions that selected for increased bacterial virulence. Our results thus suggest that quantitative host resistance was the key factor underlying the evolutionary interactions in this natural host-pathogen system.
Asunto(s)
Enfermedades de las Aves/microbiología , Pinzones , Infecciones por Mycoplasma/veterinaria , Mycoplasma gallisepticum/patogenicidad , Animales , Evolución Biológica , Modelos Biológicos , Infecciones por Mycoplasma/microbiología , Mycoplasma gallisepticum/genética , Virulencia/genéticaRESUMEN
Introduction: Surveillance is vital for monitoring the increasing risk of antimicrobial resistance (AMR) in bacteria leading to failures in humans and animals to treat infections. In a One Health context, AMR bacteria from livestock and food can transfer through the food chain to humans, and vice versa, which can be characterized in detail through genomics. We investigated the critical aspects of AMR and the dynamics of AMR in poultry in the UK. Methods: In this study, we performed whole genome sequencing for genomic characterization of 761 extended-spectrum cephalosporinases (ESCs) harboring Escherichia coli isolated from poultry caeca and meat through EU harmonized monitoring of AMR in zoonotic and commensal bacteria from 2016 and 2018 and UK national monitoring in 2020. Results: The most common ESC in 2016 and 2018 was blaCTX-M-1; however, 2020 had a greater diversity of ESCs with blaCTX-M-55 dominant in chickens and blaCTX-M-15 more prevalent in turkeys. Co-resistance to sulphonamides, tetracycline, and trimethoprim was widespread, and there were several positive correlations between the sequence types (STs) and ESC genes. We identified certain AMR genotypes and STs that were frequent each year but not as successful in subsequent years, e.g., ST350 harboring blaCTX-M-1, sul2, and tetA-v4.Phylogenetic comparison of isolates prevalent in our panel with global ones from the same STs available in public databases showed that isolates from the UK generally clustered together, suggesting greater within-country than between-country transmission. Discussion: We conclude that future genomic surveillance of indicator organisms will be invaluable as it will enable detailed comparisons of AMR between and within neighboring countries, potentially identifying the most successful sequence types, plasmids, or emerging threats.
RESUMEN
Quantifying variation in the ability to fight infection among free-living hosts is challenging and often constrained to one or a few measures of immune activity. While such measures are typically taken to reflect host resistance, they can also be shaped by pathogen effects, for example, if more virulent strains trigger more robust immune responses. Here, we test the extent to which pathogen-specific antibody levels, a commonly used measure of immunocompetence, reflect variation in host resistance versus pathogen virulence, and whether these antibodies effectively clear infection. House finches (Haemorhous mexicanus) from resistant and susceptible populations were inoculated with > 50 isolates of their novel Mycoplasma gallisepticum pathogen collected over a 20-year period during which virulence increased. Serum antibody levels were higher in finches from resistant populations and increased with year of pathogen sampling. Higher antibody levels, however, did not subsequently give rise to greater reductions in pathogen load. Our results show that antibody responses can be shaped by levels of host resistance and pathogen virulence, and do not necessarily signal immune clearance ability. While the generality of this novel finding remains unclear, particularly outside of mycoplasmas, it cautions against using antibody levels as implicit proxies for immunocompetence and/or host resistance.
Asunto(s)
Formación de Anticuerpos/fisiología , Infecciones Bacterianas/inmunología , Pinzones , Virulencia/fisiología , Animales , Infecciones Bacterianas/patología , Conducta Animal/fisiología , Enfermedades de las Aves/inmunología , Enfermedades de las Aves/microbiología , Progresión de la Enfermedad , Resistencia a la Enfermedad/inmunología , Femenino , Pinzones/inmunología , Pinzones/microbiología , Interacciones Huésped-Patógeno/inmunología , Masculino , Infecciones por Mycoplasma/inmunología , Infecciones por Mycoplasma/microbiología , Mycoplasma gallisepticum/inmunología , Mycoplasma gallisepticum/patogenicidadRESUMEN
Eliciting durable and protective T cell-mediated immunity in the respiratory mucosa remains a significant challenge. Polylactic-co-glycolic acid (PLGA)-based cationic pathogen-like particles (PLPs) loaded with TLR agonists mimic biophysical properties of microbes and hence, simulate pathogen-pattern recognition receptor interactions to safely and effectively stimulate innate immune responses. We generated micro particle PLPs loaded with TLR4 (glucopyranosyl lipid adjuvant, GLA) or TLR9 (CpG) agonists, and formulated them with and without a mucosal delivery enhancing carbomer-based nanoemulsion adjuvant (ADJ). These adjuvants delivered intranasally to mice elicited high numbers of influenza nucleoprotein (NP)-specific CD8+ and CD4+ effector and tissue-resident memory T cells (TRMs) in lungs and airways. PLPs delivering TLR4 versus TLR9 agonists drove phenotypically and functionally distinct populations of effector and memory T cells. While PLPs loaded with CpG or GLA provided immunity, combining the adjuvanticity of PLP-GLA and ADJ markedly enhanced the development of airway and lung TRMs and CD4 and CD8 T cell-dependent immunity to influenza virus. Further, balanced CD8 (Tc1/Tc17) and CD4 (Th1/Th17) recall responses were linked to effective influenza virus control. These studies provide mechanistic insights into vaccine-induced pulmonary T cell immunity and pave the way for the development of a universal influenza and SARS-CoV-2 vaccines.