Characterization Of Host Response Research Articles

Proteomic Analysis of Non-human Primate Peripheral Blood Mononuclear Cells During Burkholderia mallei Infection Reveals a Role of Ezrin in Glanders Pathogenesis.

Burkholderia mallei, the causative agent of glanders, is a gram-negative intracellular bacterium. Depending on different routes of infection, the disease is manifested by pneumonia, septicemia, and chronic infections of the skin. B. mallei poses a serious biological threat due to its ability to infect via aerosol route, resistance to multiple antibiotics and to date there are no US Food and Drug Administration (FDA) approved vaccines available. Induction of innate immunity, inflammatory cytokines and chemokines following B. mallei infection, have been observed in in vitro and small rodent models; however, a global characterization of host responses has never been systematically investigated using a non-human primate (NHP) model. Here, using a liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach, we identified alterations in expression levels of host proteins in peripheral blood mononuclear cells (PBMCs) originating from naïve rhesus macaques (Macaca mulatta), African green monkeys (Chlorocebus sabaeus), and cynomolgus macaques (Macaca fascicularis) exposed to aerosolized B. mallei. Gene ontology (GO) analysis identified several statistically significant overrepresented biological annotations including complement and coagulation cascade, nucleoside metabolic process, vesicle-mediated transport, intracellular signal transduction and cytoskeletal protein binding. By integrating an LC-MS/MS derived proteomics dataset with a previously published B. mallei host-pathogen interaction dataset, a statistically significant predictive protein-protein interaction (PPI) network was constructed. Pharmacological perturbation of one component of the PPI network, specifically ezrin, reduced B. mallei mediated interleukin-1β (IL-1β). On the contrary, the expression of IL-1β receptor antagonist (IL-1Ra) was upregulated upon pretreatment with the ezrin inhibitor. Taken together, inflammasome activation as demonstrated by IL-1β production and the homeostasis of inflammatory response is critical during the pathogenesis of glanders. Furthermore, the topology of the network reflects the underlying molecular mechanism of B. mallei infections in the NHP model.

Viral genomics in Ebola virus research.

Filoviruses such as Ebola virus continue to pose a substantial health risk to humans. Advances in the sequencing and functional characterization of both pathogen and host genomes have provided a wealth of knowledge to clinicians, epidemiologists and public health responders during outbreaks of high-consequence viral disease. Here, we describe how genomics has been historically used to investigate Ebola virus disease outbreaks and how new technologies allow for rapid, large-scale data generation at the point of care. We highlight how genomics extends beyond consensus-level sequencing of the virus to include intra-host viral transcriptomics and the characterization of host responses in acute and persistently infected patients. Similar genomics techniques can also be applied to the characterization of non-human primate animal models and to known natural reservoirs of filoviruses, and metagenomic sequencing can be the key to the discovery of novel filoviruses. Finally, we outline the importance of reverse genetics systems that can swiftly characterize filoviruses as soon as their genome sequences are available.

Diversity in Alternaria brassicae (Berk.) Sacc. isolates and characterization of host response in different oilseed Brassica species

Alternaria brassicae (Berk.) Sacc., a necrotrophic fungus devastating oilseed Brassica crops in India, causes up to 47% reduction in seed yield. So the study is conducting to develop the knowledge about the variability of A. brassicae in terms of cultural, morphological, pathogenic characters and their effects on different Brassica species of rapeseed mustard, for minimizing the losses caused by A. brassicae and help to stabilize the rapeseed mustard production. In variability study, all the isolates showed cultural, morphological variability. Average conidial length was maximum in isolate Ab2 (21.7μ) followed by Ab4 (20.7μ) and minimum in Ab8 (15.6μ). Septation in conidia, both horizontal and vertical also showed variation in different isolates. Finally it was revealed that smallest size of conidia in isolates Ab8 and longest size of conidia in isolates Ab4 were observed. On solid medium, maximum sporulation was observed in Ab7 followed while minimum sporulation recorded in Ab8. On liquid medium, maximum sporulation was observed in Ab7 while minimum sporulation recorded in Ab8. All the isolates showed the variability in qualitative characters i.e. spot colour, presence or absence of central point, concentric rings and yellow halo and as well as in quantitative characters i.e. incubation period and Percent Disease Index.

Characterization of Host Responses during Pseudomonas aeruginosa Acute Infection in the Lungs and Blood and after Treatment with the Synthetic Immunomodulatory Peptide IDR-1002.

Pseudomonas aeruginosa is an opportunistic pathogen that causes nosocomial pneumonia and infects patients with cystic fibrosis. P. aeruginosa lung infections are difficult to treat due to bacterial resistance to antibiotics, and strains with multidrug resistance are becoming more prevalent. Here, we examined the use of a small host defense peptide, innate defense regulator 1002 (IDR-1002), in an acute P. aeruginosa lung infection in vivo IDR-1002 significantly reduced the bacterial burden in bronchoalveolar lavage fluid (BALF), as well as MCP-1 in BALF and serum, KC in serum, and interleukin 6 (IL-6) in BALF. Transcriptome sequencing (RNA-Seq) was conducted on lungs and whole blood, and the effects of P. aeruginosa, IDR-1002, and the combination of P. aeruginosa and IDR-1002 were evaluated. Differential gene expression analysis showed that P. aeruginosa increased multiple inflammatory and innate immune pathways, as well as affected hemostasis, matrix metalloproteinases, collagen biosynthesis, and various metabolism pathways in the lungs and/or blood. Infected mice treated with IDR-1002 had significant changes in gene expression compared to untreated infected mice, with fewer differentially expressed genes associated with the inflammatory and innate immune responses to microbial infection, and treatment also affected morphogenesis, certain metabolic pathways, and lymphocyte activation. Overall, these results showed that IDR-1002 was effective in treating P. aeruginosa acute lung infections and associated inflammation.

Comment to: Characterization of host response, resorption, and strength properties, and performance in the presence of bacteria for fully absorbable biomaterials for soft tissue repair. Stoikes NFN, Scott J, Badhwar A, Deeken C, Voeller G.

Comment to: Characterization of host response, resorption, and strength properties, and performance in the presence of bacteria for fully absorbable biomaterials for soft tissue repair. Stoikes NFN, Scott J, Badhwar A, Deeken C, Voeller G.

Characterization of host response, resorption, and strength properties, and performance in the presence of bacteria for fully absorbable biomaterials for soft tissue repair

PurposeThe objective was to evaluate the host response, resorption, and strength properties, and to assess the performance in the presence of bacteria for Phasix™ Mesh (Phasix™) and Gore® Bio-A® Tissue Reinforcement (Bio-A®) in preclinical models.MethodsIn a rat model, one mesh (2 × 2 cm) was implanted subcutaneously in n = 60 rats. Animals were euthanized after 2, 4, 8, 12, 16, or 24 weeks (n = 5/mesh/time point), and implant sites were assessed for host inflammatory response and overall fibrotic repair thickness. In a rabbit model, meshes (3.8 cm diameter) were bilaterally implanted in subcutaneous pockets in n = 20 rabbits (n = 10 rabbits/mesh) and inoculated with 108 CFU clinically isolated methicillin-resistant Staphylococcus aureus (MRSA). One mesh type was implanted per animal. Animals were euthanized after 7 days, and implants were assessed for abscess formation, bacterial colonization, and mechanical strength.ResultsIn the rat study, Phasix™ and Bio-A® exhibited similar biocompatibility, although Bio-A® demonstrated a significantly greater inflammatory response at 4 weeks compared to Phasix™ (p < 0.01). Morphometric analysis demonstrated rapid resorption of Bio-A® implants with initially thicker repair sites at 2, 4, 8, and 12 weeks (p < 0.0001), which transitioned to significantly thinner sites compared to Phasix™ at 16 and 24 weeks (p < 0.0001). In the rabbit bacterial inoculation study, Phasix™ exhibited significantly lower abscess score (p < 0.001) and bacterial colonization (p < 0.01), with significantly greater mechanical strength than Bio-A® (p < 0.001).ConclusionsHost response, resorption, repair thickness, strength, and bacterial colonization suggest a more stable and favorable outcome for monofilament, macroporous devices such as Phasix™ relative to multifilament, microporous devices such as Bio-A® over time.

Characterization of host response to Cryptococcus neoformans through quantitative proteomic analysis of cryptococcal meningitis co-infected with HIV.

Cryptococcal meningitis is the most common opportunistic fungal infection causing morbidity and mortality (>60%) in HIV-associated immunocompromised individuals caused by Cryptococcus neoformans. Molecular mechanisms of cryptococcal infection in brain have been studied using experimental animal models and cell lines. There are limited studies for the molecular understanding of cryptococcal meningitis in human brain. The proteins involved in the process of invasion and infection in human brain still remains obscure. To this end we carried out mass spectrometry-based quantitative proteomics of frontal lobe brain tissues from cryptococcal meningitis patients and controls to identify host proteins that are associated with the pathogenesis of cryptococcal meningitis. We identified 317 proteins to be differentially expressed (≥2-fold) from a total of 3423 human proteins. We found proteins involved in immune response and signal transduction to be differentially expressed in response to cryptococcal infection in human brain. Immune response proteins including complement factors, major histocompatibility proteins, proteins previously known to be involved in fungal invasion to brain such as caveolin 1 and actin were identified to be differentially expressed in cryptococcal meningitis brain tissues co-infected with HIV. We also validated the expression status of 5 proteins using immunohistochemistry. Overexpression of major histocompatibility complexes, class I, B (HLA-B), actin alpha 2 smooth muscle aorta (ACTA2) and caveolin 1 (CAV1) and downregulation of peripheral myelin protein 2 (PMP2) and alpha crystallin B chain (CRYAB) in cryptococcal meningitis were confirmed by IHC-based validation experiments. This study provides the brain proteome profile of cryptococcal meningitis co-infected with HIV for a better understanding of the host response associated with the disease.

Immunohistological, microscopical and neurochemical studies on encephalitides. 7. Subacute sclerosing panencephalitis. Susceptibility of dogs to the virus, and characterization of host response.

Summary. LEC virus derived from a patient with SSPE was inoculated intracerebrally into beagle puppies. All three animals that received cell-associated virus and two of three animals inoculated with cell-free virus developed encephalitis. None of the other animals inoculated with cell-free and cell-associated wild measles or attenuated measles virus developed any disease. Whereas the animals that received inoculation of measles virus developed an antibody response, the animals with encephalitis due to the SSPE virus remained free of antibodies up to the point of death. These results are consistent with those previously reported by us for calves and lambs.