Dissemination Of Pathogens Research Articles

Stepping-stones and Mediators of Pandemic Expansion—A Context for Humans as Ecological Super-spreaders

Humans represent ecological super-spreaders in the dissemination and introduction of pathogens. These processes, consistent with the dynamics of the Stockholm paradigm, are exemplified in the origin and globalized distributions of SARS-CoV-2 since initial recognition in central Asia during 2019 and 2020. SARS-like viruses are not widespread in mammals but appear widespread in chiropterans. Bats are isolated ecologically from most other assemblages of mammals in terrestrial systems. Humans may be the stepping-stone hosts for broad global dissemination and wider infection (given the opportunity) among diverse assemblages of mammals in which host and viral capacity are compatible. Human globalization mediated insertion in global ecosystems along primary and secondary pathways initially with localized to regional circulation across continents. Origins and persistence of cycles involving variants and viral transmission among other mammals and the potential for secondary exposure (retrocolonization) of people occurs on multidirectional pathways. Humans were responsible for the initial breakdown in ecological isolation of the virus that facilitated colonization events from chiropterans to other mammals. In the absence of these human drivers, environmental or ecological interfaces (boundary zones among habitats) limiting the distribution of SARS-CoV-2 are unlikely to have been crossed, leaving a diverse assemblage of SARS-like viruses (Sarbecovirus) remaining relatively hidden and isolated in southeast Asia.

Impact of Calonectria Diseases on Ornamental Horticulture: Diagnosis and Control Strategies.

Diseases caused by fungi in the genus Calonectria pose a significant threat to the ornamental horticulture industries in Europe and the United States. Calonectria spp. are particularly challenging pathogens to manage in ornamental production systems and the urban landscape for multiple reasons. A high level of species diversity and poorly resolved taxonomy in the genus makes proper pathogen identification and disease diagnosis a challenge, though recent molecular phylogenetic studies have made significant advances in species delimitation. From a disease management perspective, Calonectria spp. produce long-lived survival structures (microsclerotia) that contaminate nursery production systems and can survive multiple years in the absence of a susceptible plant host. Latent infection of plant material is poorly understood but likely contributes to long-distance dissemination of these fungal pathogens, including the clonal Calonectria spp. responsible for the global emergence of boxwood blight. Breeding for disease resistance represents a sustainable strategy for managing Calonectria diseases but is challenging due to the perennial nature of many ornamental plants and high levels of susceptibility in commercial cultivars. Ultimately, long-term sustainable management of Calonectria diseases will require an improved understanding of pathogen biology as well as integration of multiple disease management strategies.

ASSESSMENT OF MICROBIOLOGICAL QUALITY OF SOYMILK BEVERAGE

This research work is aimed at evaluating microbial quality of soy milk taken by the populace in Enugu and verifying the safety standard of soymilk consumed by Nigerians in general. A collection of ten samples of soy milk locally sourced and produced by their makers were used for this research. The pour plate method was used to determine number of microbes present as well as the identity of the microbes. Biochemical tests were carried out on the isolates to determine using standard techniques. The microbial count and types of isolates showed a low hygienic standard of soymilk production, which will in turn result to a public health problem among the numerous consumers. The soymilk samples were seen to contain disease-causing bacteria like Staphylococcus aureus. This research shows that the quality of some of the commercially marketed soymilk products sold in Enugu, Nigeria needs to be properly analysed in respect to evaluation of its quality to avoid dissemination of diseases or pathogens to final consumers. It is important also, that manufacturers of these soymilk products must be properly educated about Good Manufacturing Practices (GMP) as this will ensure that products are free of disease-causing microorganisms. Examination for microbial contaminants showed bacterial counts as high as 8.2 x 102 CFU/ml. The study showed some level of contamination of the selected samples with fecal coliforms such as Escherichia coli. Staphylococcus aureus was also reported in some samples. These findings reflect low hygienic standards of production, which causes public health problems in the population.

Effects of habitat and sampling time on bacterial community composition and diversity in the gut of the female house fly, Musca domestica Linnaeus (Diptera: Muscidae).

Adult house flies feed and breed in a variety of microbe-rich habitats and serve as vectors for human and animal pathogens. To better understand their role in harbouring and disseminating bacteria, we characterized the composition and diversity of bacterial communities in the gut of female house flies collected from three different habitats in Kansas: agricultural (dairy farm), urban (business area dumpsters) and mixed (business located between residential and animal agriculture areas). Bacterial community composition and diversity were influenced more by the house flies' habitat than by sampling time. The most abundant taxa were also highly prevalent in the house flies collected from all three habitats, potentially representing a 'core microbiome' attributable to the fly's trophic and reproductive associations with substrates and food sources comprised of decaying matter and/or animal waste. Bacterial taxa associated with vertebrate guts/faeces and potential pathogens were highly abundant in agricultural fly microbial communities. Interestingly, taxa of potential pathogens were highly abundant in flies from the mixed and urban sites. House flies harboured diverse bacterial communities influenced by the habitat in which they reside, including potential human and animal pathogens, further bolstering their role in the dissemination of pathogens, and indicating their utility for pathogen surveillance.

"Migratory beekeeping and its influence on the prevalence and dispersal of pathogens to managed and wild bees".

Demand for food is growing along with the human population, leading to an increase in plant production. Many crops are pollinated by insects, so the global demand for managed pollinators is also increasing. The honey bee has traditionally been considered the main provider of crop pollination services. For providing it beekeepers seasonally transport hives to different locations after the flowering of different crops. These movements could be detrimental to pollinators by: i) stressing honey bees, making them more susceptible to pathogens and parasites; ii) spreading bee parasites and pathogens across locations; iii) increasing the transmission of parasites and pathogens between managed and wild pollinators and vice versa (spillover and spillback, respectively). To understand the impact of migratory beekeeping on bee health, we conducted a systematic review to identify the main trends and provide a complete picture of existing knowledge on the subject. We found 52 studies analysing pathogen-related impacts of migratory beekeeping on honey bees. However, only 16 investigations tested the effect of migratory practices on the prevalence and spread of pathogens and parasites. We found no studies that assessed the impact of migratory beekeeping on the occurrence and spread of pests and diseases in wild bees. In general, migratory beekeeping tends to increase the prevalence of pathogens and parasites in honey bee colonies. However, the results were very heterogeneous, probably due to several uncontrolled underlying factors such as management, biological and geographical factors, and the interactions between them. In conclusion, there is an urgent need for studies to assess the impact of migratory beekeeping on bee health, given the current global bee decline and the expected increase in migratory beekeeping due to climate change and crop pollination demand.

Investigating the microbiological risks associated with urban flooding in the UK

Over the last 30 years, the frequency and occurrence of intense rainfall, and thus extreme hydrological events –flooding- has steadily increased. Drainage infrastructure in the UK was not designed for a changing climate, and many sewer systems in densely populated urban areas, are unable to cope. Sewage overflow and surface run off in urban areas can act as vectors for the dissemination of pathogens, known to cause disease among human populations. Most of the previous studies in this field have focused on using faecal indicators such as E.coli when assessing the public health risk of floodwater [1]. However, traditional indicators do not accurately reflect the true risk that urban flooding poses [2]. Little is understood in regards to the survivability and behaviour of pathogens in different urban settings, which are fundamental to determine potential risks to public health. Previous investigations in UK waterlogged soils have shown a clear response of microbial communities to water table variation, temperature, and nutrient availability in soil profiles [3]. This research aims to investigate, using advanced molecular methods, the dynamics of pathogens (i.e. movement through soil and survival rates), and microbial interactions at the soil/water interface- collecting information from field work studies and laboratory-controlled experiments. The outcomes from this research will inform future management strategies of flooded sites that will aid to protect public health.

Impact of sink design on bacterial transmission from hospital sink drains to the surrounding sink environment tested using a fluorescent marker

In hospitals, sinks act as reservoirs for bacterial pathogens. To assess the extent of splashing, fluorescein dye was added to four hospital sinks previously involved in pathogen dispersal to the environment and/or transmission to patients, and one sink that was not. Applying dye to the p-trap or tailpiece did not result in any fluorescent droplets outside of the drain. When applied to the drain, droplets were found in all but one wash basin, and this was more common in the absence of a drain plug. Sink design considerations to install drain plugs, reduce dripping and offset the tap may help to prevent transmission from drains.

Effects of planted pollinator habitat on pathogen prevalence and interspecific detection between bee species

Shared resources can instigate pathogen spread due to large congregations of individuals in both natural and human modified resources. Of current concern is the addition of pollinator habitat in conservation efforts as it attracts bees of various species, potentially instigating interspecific sharing of pathogens. Common pathogens have been documented across a wide variety of pollinators with shared floral resources instigating their spread in some, but not all, cases. To evaluate the impact of augmented pollinator habitat on pathogen prevalence, we extracted RNA from samples of eight bee species across three families and screened these samples for nine pathogens using RT-qPCR. We found that some habitat characteristics influenced pathogen detection; however, we found no evidence that pathogen detection in one bee species was correlated with pathogen detection in another. In fact, pathogen detection was rare in wild bees. While gut parasites were detected in 6 out of the 8 species included in this study, viruses were only detected in honey bees. Further, virus detection in honey bees was low with a maximum 21% of samples testing positive for BQCV, for example. These findings suggest factors other than the habitat itself may be more critical in the dissemination of pathogens among bee species. However, we found high relative prevalence and copy number of gut parasites in some bee species which may be of concern, such as Bombus pensylvanicus. Long-term monitoring of pathogens in different bee species at augmented pollinator habitat is needed to evaluate if these patterns will change over time.

AscotraceR: An R Package Resource to Simulate the Spatiotemporal Spread of Ascochyta Blight in a Chickpea Field Over a Growing Season.

ascotraceR: An R Package Resource to Simulate the Spatiotemporal Spread of Ascochyta Blight in a Chickpea Field Over a Growing Season.

Electrolytic Disinfection of Irrigation Water for Intensive Crop Production in Greenhouses as Demonstrated on Tomatoes (Solanum lycopersicum Mill)

Shortage of water availability and awareness of the need for sustainable resource management have generated a significant increase in the use of recycled water for irrigation and processing of crops and harvest products, respectively. As a result, irrigation systems face the challenge of neutralizing plant pathogens to reduce the risk of their dispersal and the subsequent occurrence of diseases with potentially high economic impacts. We evaluated the efficacy of an innovative electrolytic disinfection system based on potassium hypochlorite (KCLO) to inactivate major pathogens in hydroponically grown tomatoes: Fusarium oxysporum (Synder and Hans), Rizocthonia solani (Kühn), Tobacco mosaic virus (TMV) and Pepino mosaic virus (PepMV). The electrolytically derived disinfectant was prepared on-site and added to the recirculating fertigation solution once a week for 60 min in an automated manner using sensor technology at a dosage of 0.5 mg of free chlorine/L (fertigation solution at pH 6.0 ± 0.3 and ORP 780 ± 31 mV). Tomato fruit yield and pathogen dispersal were determined for 16 weeks. At the applied dosage, the disinfectant has been shown to inhibit the spread of plant pathogenic fungi and, remarkably, plant viruses in recirculating fertigation solutions. Phytotoxic effects did not occur.

Insights Gained Into the Treatment of COVID19 by Pulmonary Surfactant and Its Components.

Pulmonary surfactant constitutes an important barrier that pathogens must cross to gain access to the rest of the organism via the respiratory surface. The presence of pulmonary surfactant prevents the dissemination of pathogens, modulates immune responses, and optimizes lung biophysical activity. Thus, the application of pulmonary surfactant for the treatment of respiratory diseases provides an effective strategy. Currently, several clinical trials are investigating the use of surfactant preparations to treat patients with coronavirus disease 2019 (COVID-19). Some factors have been considered in the application of pulmonary surfactant for the treatment COVID-19, such as mechanical ventilation strategy, timing of treatment, dose delivered, method of delivery, and preparation utilized. This review supplements this list with two additional factors: accurate measurement of surfactants in patients and proper selection of pulmonary surfactant components. This review provides a reference for ongoing exogenous surfactant trials involving patients with COVID-19 and provides insight for the development of surfactant preparations for the treatment of viral respiratory infections.

Essential role for epithelial HIF‐xenophagy axis in control of Salmonella infection and dissemination

The intestinal mucosa exists in a state of “physiologic hypoxia,” in which oxygen tensions of the epithelium and lumen are markedly lower than those encountered in other tissues. Intestinal epithelial cells (IECs) have evolved to maintain mucosal homeostasis in this austere environment in part through the actions of dedicated oxygen‐sensitive transcription factors, including hypoxia‐inducible factors (HIFs). HIFs are composed of a labile α‐subunit that becomes stabilized most notably in hypoxic environments and a constitutive β‐subunit. Using an unbiased chromatin immunoprecipitation (ChIP) promoter array screen for HIF‐1 targets in IEC, we identified autophagy as a major pathway induced by hypoxia and HIF in cultured IECs. Autophagy is a conserved eukaryotic system for degradation of intracellular cargo through the lysosome. Validation of the ChIP screen revealed that HIF promotes expression of multiple autophagy genes in IEC cell lines and further validated in primary murine organoids. One important function of autophagy is to defend against intracellular pathogens, a process termed xenophagy, a crucial innate immune mechanism in the mucosa that serves to control invasion of intracellular bacteria in vivo and to limit extraintestinal dissemination of enteric pathogens. Loss of function analysis revealed that HIF is a central regulator of autophagic flux and that in vitro infection of IECs with SalmonellaTyphimurium, a model intracellular bacterial pathogen, results in stabilization of HIF with the subsequent increase in HIF transcriptional activity that tracks with the clearance of intracellular Salmonella. Studies in vivo revealed that Salmonella­ drives increases in HIF activity using HIF luciferase reporter mice (HIF∆ODD) in combination with streptomycin‐pretreatment model of murine colitis. Further studies in vivo demonstrated that intestinal epithelial‐specific deletion of HIF (Hif1b∆IEC) compromised IEC xenophagy and exacerbated bacterial dissemination to multiple extraintestinal organs, implicating xenophagy‐assisted clearance of Salmonella in mucosal innate immunity.

Environmental Risk Factors in the Human Pathogen Transmission Pathways between Animal Operations and Produce Crops

Once zoonotic pathogens leave their animal hosts, how they move through the environment and are deposited on unharvested produce remains a persistent industry challenge and research question related to produce safety. The proximity of animals to production areas, animal types and densities, an animal operation’s management practices, and weather conditions are some of the areas explored by researchers to better understand how pathogens contaminate unharvested crops. Water, inputs, airborne particulates, wildlife, and insects may serve as vectors linking pathogens from their animal hosts to produce production areas. Studies have shown a positive correlation between rainfall and pathogen concentrations in agricultural water downstream from animal operations. Bacteria attached to airborne particulates can be deposited onto crops or open water sources. Wildlife and insects share habitat with domesticated animals in rangelands, pasture settings, pens, and feedlots. Plant conditions (injuries, disease) and characteristics (surface topography, genetic traits, age, native microbiota) and environmental conditions (relative humidity, moisture, temperature) play a major role in determining pathogen survival on unharvested produce. This article explores recent research findings elucidating human pathogen dispersion and deposition, subsequent transfer from animals to crops, and the various environmental risk factors along the way that play a role.

Blood vessel occlusion by Cryptococcus neoformans is a mechanism for haemorrhagic dissemination of infection.

Meningitis caused by infectious pathogens is associated with vessel damage and infarct formation, however the physiological cause is often unknown. Cryptococcus neoformans is a human fungal pathogen and causative agent of cryptococcal meningitis, where vascular events are observed in up to 30% of patients, predominantly in severe infection. Therefore, we aimed to investigate how infection may lead to vessel damage and associated pathogen dissemination using a zebrafish model that permitted noninvasive in vivo imaging. We find that cryptococcal cells become trapped within the vasculature (dependent on their size) and proliferate there resulting in vasodilation. Localised cryptococcal growth, originating from a small number of cryptococcal cells in the vasculature was associated with sites of dissemination and simultaneously with loss of blood vessel integrity. Using a cell-cell junction tension reporter we identified dissemination from intact blood vessels and where vessel rupture occurred. Finally, we manipulated blood vessel tension via cell junctions and found increased tension resulted in increased dissemination. Our data suggest that global vascular vasodilation occurs following infection, resulting in increased vessel tension which subsequently increases dissemination events, representing a positive feedback loop. Thus, we identify a mechanism for blood vessel damage during cryptococcal infection that may represent a cause of vascular damage and cortical infarction during cryptococcal meningitis.

Staphylococcus aureus α-Toxin Effect on Acinetobacter baumannii Behavior.

Simple SummaryPolymicrobial infections, infections that are caused by more than one pathogen, are known to be responsible associated with high mortality rates. The bacterial organisms involved in these infections favor each other, resulting in pathogens’ success. Our work examined the behavioral response of Acinetobacter baumannii after exposure to cell-free conditioned media of Staphylococcus aureus, two pathogens responsible for severe infections. We focus on the effect of α-toxin, the primary cytotoxic agent released by S. aureus, on A. baumannii’s behavior. Results indicated that α-toxin contributes to the proliferation and survival of A. baumannii. One or more soluble molecules secreted by S. aureus can be sensed by A. baumannii and trigger diverse responses to adapt to environmental changes. The coexistence between bacteria can result in modifications in their general biology.Polymicrobial infections are more challenging to treat and are recognized as responsible for significant morbidity and mortality. It has been demonstrated that multiple Gram-negative organisms take advantage of the effects of Staphylococcus aureus α-toxin on mucosal host defense, resulting in proliferation and dissemination of the co-infecting pathogens. Through phenotypic approaches, we observed a decrease in the motility of A. baumannii A118 after exposure to cell-free conditioned media (CFCM) of S. aureus strains, USA300 and LS1. However, the motility of A. baumannii A118 was increased after exposure to the CFCM of S. aureus strains USA300 Δhla and S. aureus LSI ΔagrA. Hemolytic activity was seen in A118, in the presence of CFCM of S. aureus LS1. Further, A. baumannii A118 showed an increase in biofilm formation and antibiotic resistance to tetracycline, in the presence of CFCM of S. aureus USA300. Transcriptomic analysis of A. baumannii A118, with the addition of CFCM from S. aureus USA300, was carried out to study A. baumannii response to S. aureus’ released molecules. The RNA-seq data analysis showed a total of 463 differentially expressed genes, associated with a wide variety of functions, such as biofilm formation, virulence, and antibiotic susceptibility, among others. The present results showed that A. baumannii can sense and respond to molecules secreted by S. aureus. These findings demonstrate that A. baumannii may perceive and respond to changes in its environment; specifically, when in the presence of CFCM from S. aureus.

Induced antigen-binding polyreactivity in human serum IgA

Previous studies have shown that polyreactive antibodies play an important role in the frontline defense against the dissemination of pathogens in the pre-immune host. Interestingly, antigen-binding polyreactivity can not only be inherent, but also acquired post-translationally. The ability of individual monoclonal IgG and IgE antibodies to acquire polyreactivity following contact with various agents that destabilize protein structure (urea, low pH) or have a pro-oxidative potential (heme, ferrous ions) has been studied in detail. However, to the best of our knowledge this property of human IgA has previously been described only cursorily. In the present study pooled human serum IgA and two human monoclonal IgA antibodies were exposed to buffers with acidic pH, to free heme or to ferrous ions, and the antigen-binding behavior of the native and modified IgA to viral and bacterial antigens were compared using immunoblot and ELISA. We observed a dose-dependent increase in reactivity to several bacterial extracts and to pure viral antigens. This newly described property of IgA may have therapeutic potential as has already been shown for pooled IgG with induced polyreactivity.

Predicting the impact of environmental factors on citrus canker through multiple regression.

Climatic conditions play a significant role in the development of citrus canker caused by Xanthomonas citri pv. citri (Xcc). Citrus canker is regarded as one of the major threats being faced by citrus industry in citrus growing countries of the world. Climatic factors exert significant impacts on growth stage, host susceptibility, succulence, vigor, survival, multiplication rate, pathogen dispersion, spore penetration rate, and spore germination. Predicting the impacts of climatic factors on these traits could aid in the development of effective management strategies against the disease. This study predicted the impacts of environmental variables, i.e., temperature, relative humidity, rainfall, and wind speed the development of citrus canker through multiple regression. These environmental variables were correlated with the development of canker on thirty (30) citrus varieties during 2017 to 2020. Significant positive correlations were noted among environment variables and disease development modeled through multiple regression model (Y = +24.02 + 0.5585 X1 + 0.2997 X2 + 0.3534 X3 + 3.590 X4 + 1.639 X5). Goodness of fit of the model was signified by coefficient determination value (97.5%). Results revealed the optimum values of environmental variables, i.e., maximum temperature (37°C), minimum temperature (27°C), relative humidity (55%), rainfall (4.7–7.1 mm) and wind speed (8 Km/h), which were conducive for the development of citrus canker. Current study would help researchers in designing better management strategies against citrus canker disease under changing climatic conditions in the future.

SARS-CoV-2 Spike Protein and Mouse Coronavirus Inhibit Biofilm Formation by Streptococcus pneumoniae and Staphylococcus aureus

The presence of co-infections or superinfections with bacterial pathogens in COVID-19 patients is associated with poor outcomes, including increased morbidity and mortality. We hypothesized that SARS-CoV-2 and its components interact with the biofilms generated by commensal bacteria, which may contribute to co-infections. This study employed crystal violet staining and particle-tracking microrheology to characterize the formation of biofilms by Streptococcus pneumoniae and Staphylococcus aureus that commonly cause secondary bacterial pneumonia. Microrheology analyses suggested that these biofilms were inhomogeneous soft solids, consistent with their dynamic characteristics. Biofilm formation by both bacteria was significantly inhibited by co-incubation with recombinant SARS-CoV-2 spike S1 subunit and both S1 + S2 subunits, but not with S2 extracellular domain nor nucleocapsid protein. Addition of spike S1 and S2 antibodies to spike protein could partially restore bacterial biofilm production. Furthermore, biofilm formation in vitro was also compromised by live murine hepatitis virus, a related beta-coronavirus. Supporting data from LC-MS-based proteomics of spike–biofilm interactions revealed differential expression of proteins involved in quorum sensing and biofilm maturation, such as the AI-2E family transporter and LuxS, a key enzyme for AI-2 biosynthesis. Our findings suggest that these opportunistic pathogens may egress from biofilms to resume a more virulent planktonic lifestyle during coronavirus infections. The dispersion of pathogens from biofilms may culminate in potentially severe secondary infections with poor prognosis. Further detailed investigations are warranted to establish bacterial biofilms as risk factors for secondary pneumonia in COVID-19 patients.

The role of pipe biofilms on dissemination of viral pathogens and virulence factor genes in a full-scale drinking water supply system

Water is an important medium for virus transmission and viral pathogens are increasingly appreciated as a significant water safety issue. However, the effect of pipe biofilms on viral pathogens remains unclear. This research aimed to investigate the dissemination of viruses in a full-scale drinking water supply system (DWSS) and the effect of pipe biofilms on viral pathogens in bulking water. Viral pathogens, pathogenic viral hosts, and viral virulence factors (VFs) were found to disseminate from source water to tap water. The proportion of virus and viral VFs in the biofilm was far less than that in water. The contribution of biofilms in pipe wall to viruses and viral VFs in bulking water was less than 4%, and viruses in the biofilm had no obvious effect on pathogenic viruses in water. Dominant viruses carrying VFs changed from Cyanobacteria virus to Mycobacterium virus after advanced water treatment. Mycobacterium and organics were identified as the key factors influencing composition and abundance of viral VFs, which could explain 41.1% of the variation in viral virulence in the water supply system. Host bacteria and organics may be used as the key targets to control the risk of viruses in DWSSs.

The Induced Immune Response in Patients With Infectious Spondylodiscitis: A Prospective Observational Cohort Study.

IntroductionInfectious spondylodiscitis is a rare infection of the intervertebral disc and the adjacent vertebral bodies that often disseminates and requires long-term antibiotic therapy. Immunologic profiling of patients with infectious spondylodiscitis could allow for a personalized medicine strategy. We aimed to examine the induced immune response in patients with infectious spondylodiscitis during and after antibiotic therapy. Furthermore, we explored potential differences in the induced immune response depending on the causative pathogen and the dissemination of the disease.MethodsThis was a prospective observational cohort study that enrolled patients with infectious spondylodiscitis between February 2018 and August 2020. A blood sample was collected at baseline, after four to six weeks of antibiotic therapy (during antibiotic therapy), and three to seven months after end of antibiotic therapy (post-infection). The induced immune response was assessed using the standardized functional immune assay TruCulture®. We used a panel of three immune cell stimuli (lipopolysaccharide, Resiquimod and polyinosinic:polycytodylic acid) and an unstimulated control. For each stimulus, the induced immune response was assessed by measuring the released concentration of Interleukin (IL)-1β, IL-6, IL-8, IL-10, IL-12p40, IL-17A, Interferon-γ (IFN-γ) and Tumor necrosis factor-α (TNF-α) in pg/mL.ResultsIn total, 49 patients with infectious spondylodiscitis were included. The induced immune responses were generally lower than references at baseline, but the cytokine release increased in patients after treatment with antibiotic therapy. Post-infection, most of the released cytokine concentrations were within the reference range. No significant differences in the induced immune responses based on stratification according to the causative pathogen or dissemination of disease were found.ConclusionWe found lower induced immune responses in patients with infectious spondylodiscitis at baseline. However, post-infection, the immune function normalized, indicating that an underlying immune deficiency is not a prominent factor for spondylodiscitis. We did not find evidence to support the use of induced immune responses as a tool for prediction of the causative pathogen or disease dissemination, and other methods should be explored to guide optimal treatment of patients with infectious spondylodiscitis.