scholarly journals PET Study of Sphingosine-1-phosphate Receptor 1 Expression in Response to S. aureus Infection

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Hao Jiang ◽  
Jiwei Gu ◽  
Haiyang Zhao ◽  
Sumit Joshi ◽  
Joel S. Perlmutter ◽  
...  
Keyword(s):  
Immune Response ◽  
Infectious Diseases ◽  
Bacterial Infection ◽  
Normal Control ◽  
Ex Vivo ◽  
Influenza Viruses ◽  
Aureus Infection ◽  
Early Immune Response ◽  
Sphingosine 1 Phosphate ◽  
Ex Vivo Biodistribution

Sphingosine-1-phosphate receptor 1 (S1PR1) plays a crucial role in infectious diseases. Targeting S1PR1 provides protection against pathogens, such as influenza viruses. This study is aimed at investigating S1PR1 in response to bacterial infection by assessing S1PR1 expression in S. aureus-infected mice. A rodent local muscle bacterial infection model was developed by injecting S. aureus to the lower hind limb of Balb/c mice. The changes of S1PR1 expression in response to bacterial infection and blocking treatment were assessed using ex vivo biodistribution and in vivo positron emission tomography (PET) after intravenous injection of an S1PR1-specific radiotracer [18F]TZ4877. The specificity of [18F]TZ4877 was assessed using S1PR1-specific antagonist, NIBR-0213, and S1PR1-specific DsiRNA pretreated the animals. Immunohistochemical studies were performed to confirm the increase of S1PR1 expression in response to infection. Ex vivo biodistribution data showed that the uptake of [18F]TZ4877 was increased 30.6%, 54.3%, 74.3%, and 115.3% in the liver, kidney, pancreas, and thymus of the infected mice, respectively, compared to that in normal control mice, indicating that S1PR1 is involved in the early immune response to bacterial infection. NIBR-0213 or S1PR1-specific DsiRNA pretreatment reduced the tissue uptake of [18F]TZ4877, suggesting that uptake of [18F]TZ4877 is specific. Our PET/CT study data also confirmed that infected mice have increased [18F]TZ4877 uptake in several organs comparing to that in normal control mice. Particularly, compared to control mice, a 39% increase of [18F]TZ4877 uptake was observed in the infected muscle of S. aureus mice, indicating that S1PR1 expression was directly involved in the inflammatory response to infection. Overall, our study suggested that S1PR1 plays an important role in the early immune response to bacterial infection. The uptake of [18F]TZ4877 is tightly correlated with the S1R1 expression in response to S. aureus infection. PET with S1PR1-specific radiotracer [18F]TZ4877 could provide a noninvasive tool for detecting the early S1PR1 immune response to infectious diseases.

scholarly journals 408. Single-cell Sequencing Identifies Variability in Host Response Among Different Genera of Influenza Viruses

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S207-S207
Author(s):  
Beth Kristine Thielen ◽  
Jaime Christensen ◽  
Anna K. Strain ◽  
Steven Shen ◽  
Ryan Langlois
Keyword(s):  
Immune Response ◽  
Single Cell ◽  
Host Response ◽  
Influenza A ◽  
Influenza Viruses ◽  
Specific Cell ◽  
Initial Exposure ◽  
Single Cell Sequencing ◽  
Early Immune Response ◽  
Infected Cells

Abstract Background Seroprevalence and surveillance studies indicate that influenza C virus (ICV) infection is common among humans, and initial exposure occurs early in life. ICV often causes milder disease than influenza A and B viruses, but the mechanisms underlying differences in pathogenicity remain poorly understood. Methods To compare early events of infection in natural target sites, we cultured primary human tracheal/bronchial epithelial cells under air-liquid interface conditions to allow differentiation. We-infected these cells with human strains of influenza A, B or C virus. Cells were infected at low MOI (0.1) to ensure populations of directly infected cells and uninfected neighboring cells. To compare the early immune response and cell tropism among these viruses, we performed single-cell RNA sequencing of mock- and influenza-infected cells. In parallel, we infected cells pretreated with interferon to mimic later rounds of infection after an early immune response is initiated. Results Infection of primary cells by all three viruses was confirmed by RT-qPCR of bulk cell lysates. As expected, prior exposure to interferon β results resulted in reduced levels of viral transcripts. At the single-cell level, we identified expression of genes associated with specific cell types, including basal, ciliated and secretory cells. We also identified expression of interferon stimulated genes, but these genes were not homogeneously expressed among all cell subpopulations and varied among cultures infected with different influenza viruses. We also found different patterns in gene expression in cells previously exposed to interferon, suggesting that host environment varies over subsequent rounds of infection. Conclusion Single-cell sequencing is an important tool for studying the host response to influenza infection in complex cellular environments such as the respiratory tract, in which cells vary in their susceptibility to infection and antiviral response. Further analysis will characterize differences among directly infected vs. neighboring cells and correlate responses with pathogenicity. Disclosures All authors: No reported disclosures.

Prebiotic Carbohydrates for Therapeutics.

2020 ◽  
Vol 20 ◽  
Author(s):  
Renuka Basavaiah ◽  
Prapulla Siddalingaiya Gurudutt
Keyword(s):  
Immune Response ◽  
Lipid Metabolism ◽  
Bacterial Infection ◽  
Food Industry ◽  
Health Benefits ◽  
Well Being ◽  
Intestinal Disease ◽  
Mineral Absorption ◽  
Health Promoting ◽  
Insulin Dependent

: The food industry is constantly shifting focus based on prebiotics as health-promoting substrates rather than just food supplements. A prebiotic is ‘‘a selectively fermented ingredient that allows specific changes, both in the composition and/or activity in the gastrointestinal microflora that confers benefits upon host well-being and health.” Prebiotics exert a plethora of health-promoting effects, which has lead to the establishment of multimillion food and pharma industries. The following are the health benefits attributed to prebiotics: mineral absorption, better immune response, increased resistance to bacterial infection, improved lipid metabolism, possible protection against cancer, relief from poor digestion of lactose, and reduction in the risk of diseases such as intestinal disease, non-insulin dependent diabetes, obesity and allergy. Numerous studies in both animals and humans have demonstrated the health benefits of prebiotics.

Notch signaling pathway in infectious diseases: role in the regulation of immune response

2021 ◽  
Vol 70 (3) ◽  
pp. 261-274
Author(s):  
Ricardo Cardoso Castro ◽  
Relber Aguiar Gonçales ◽  
Fabiana Albani Zambuzi ◽  
Fabiani Gai Frantz
Keyword(s):  
Immune Response ◽  
Infectious Diseases ◽  
Notch Signaling ◽  
Signaling Pathway ◽  
Notch Signaling Pathway

scholarly journals The host transcriptional response to Candidemia is dominated by neutrophil activation and heme biosynthesis and supports novel diagnostic approaches

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Julie M. Steinbrink ◽  
Rachel A. Myers ◽  
Kaiyuan Hua ◽  
Melissa D. Johnson ◽  
Jessica L. Seidelman ◽  
...  
Keyword(s):  
Immune Response ◽  
Bacterial Infection ◽  
Viral Infection ◽  
Fungal Infection ◽  
Host Response ◽  
Hospitalized Patients ◽  
Neutrophil Activation ◽  
Heme Biosynthesis ◽  
Transcriptional Analysis ◽  
Diagnostic Approaches

Abstract Background Candidemia is one of the most common nosocomial bloodstream infections in the United States, causing significant morbidity and mortality in hospitalized patients, but the breadth of the host response to Candida infections in human patients remains poorly defined. Methods In order to better define the host response to Candida infection at the transcriptional level, we performed RNA sequencing on serial peripheral blood samples from 48 hospitalized patients with blood cultures positive for Candida species and compared them to patients with other acute viral, bacterial, and non-infectious illnesses. Regularized multinomial regression was utilized to develop pathogen class-specific gene expression classifiers. Results Candidemia triggers a unique, robust, and conserved transcriptomic response in human hosts with 1641 genes differentially upregulated compared to healthy controls. Many of these genes corresponded to components of the immune response to fungal infection, heavily weighted toward neutrophil activation, heme biosynthesis, and T cell signaling. We developed pathogen class-specific classifiers from these unique signals capable of identifying and differentiating candidemia, viral, or bacterial infection across a variety of hosts with a high degree of accuracy (auROC 0.98 for candidemia, 0.99 for viral and bacterial infection). This classifier was validated on two separate human cohorts (auROC 0.88 for viral infection and 0.87 for bacterial infection in one cohort; auROC 0.97 in another cohort) and an in vitro model (auROC 0.94 for fungal infection, 0.96 for bacterial, and 0.90 for viral infection). Conclusions Transcriptional analysis of circulating leukocytes in patients with acute Candida infections defines novel aspects of the breadth of the human immune response during candidemia and suggests promising diagnostic approaches for simultaneously differentiating multiple types of clinical illnesses in at-risk, acutely ill patients.

scholarly journals MicroRNAs: Biological Regulators in Pathogen–Host Interactions

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 113 ◽  
Author(s):  
Stephanie Maia Acuña ◽  
Lucile Maria Floeter-Winter ◽  
Sandra Marcia Muxel
Keyword(s):  
Immune Response ◽  
Infectious Diseases ◽  
Small Rnas ◽  
Immune Cell ◽  
Fine Tuning ◽  
Biological Processes ◽  
Host Interactions ◽  
The Past ◽  
Biological Aspects

An inflammatory response is essential for combating invading pathogens. Several effector components, as well as immune cell populations, are involved in mounting an immune response, thereby destroying pathogenic organisms such as bacteria, fungi, viruses, and parasites. In the past decade, microRNAs (miRNAs), a group of noncoding small RNAs, have emerged as functionally significant regulatory molecules with the significant capability of fine-tuning biological processes. The important role of miRNAs in inflammation and immune responses is highlighted by studies in which the regulation of miRNAs in the host was shown to be related to infectious diseases and associated with the eradication or susceptibility of the infection. Here, we review the biological aspects of microRNAs, focusing on their roles as regulators of gene expression during pathogen–host interactions and their implications in the immune response against Leishmania, Trypanosoma, Toxoplasma, and Plasmodium infectious diseases.

scholarly journals Checkpoint blockade accelerates a novel switch from an NKT-driven TNFα response toward a T cell driven IFN-γ response within the tumor microenvironment

2021 ◽  
Vol 9 (6) ◽  
pp. e002269
Author(s):  
Shota Aoyama ◽  
Ryosuke Nakagawa ◽  
Satoshi Nemoto ◽  
Patricio Perez-Villarroel ◽  
James J Mulé ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Tumor Growth ◽  
Ex Vivo ◽  
T Cell Response ◽  
Effector Function ◽  
Checkpoint Blockade ◽  
Necrosis Factor Alpha ◽  
Ifn Γ

BackgroundThe temporal response to checkpoint blockade (CB) is incompletely understood. Here, we profiled the tumor infiltrating lymphocyte (TIL) landscape in response to combination checkpoint blockade at two distinct timepoints of solid tumor growth.MethodsC57BL/6 mice bearing subcutaneous MC38 tumors were treated with anti-PD-1 and/or anti-CTLA-4 antibodies. At 11 or 21 days, TIL phenotype and effector function were analyzed in excised tumor digests using high parameter flow cytometry. The contributions of major TIL populations toward overall response were then assessed using ex vivo cytotoxicity and in vivo tumor growth assays.ResultsThe distribution and effector function among 37 distinct TIL populations shifted dramatically between early and late MC38 growth. At 11 days, the immune response was dominated by Tumor necrosis factor alpha (TNFα)-producing NKT, representing over half of all TIL. These were accompanied by modest frequencies of natural killer (NK), CD4+, or CD8+ T cells, producing low levels of IFN-γ. At 21 days, NKT populations were reduced to a combined 20% of TIL, giving way to increased NK, CD4+, and CD8+ T cells, with increased IFN-γ production. Treatment with CB accelerated this switch. At day 11, CB reduced NKT to less than 20% of all TIL, downregulated TNFα across NKT and CD4+ T cell populations, increased CD4+ and CD8+ TIL frequencies, and significantly upregulated IFN-γ production. Degranulation was largely associated with NK and NKT TIL. Blockade of H-2kb and/or CD1d during ex vivo cytotoxicity assays revealed NKT has limited direct cytotoxicity against parent MC38. However, forced CD1d overexpression in MC38 cells significantly diminished tumor growth, suggesting NKT TIL exerts indirect control over MC38 growth.ConclusionsDespite an indirect benefit of early NKT activity, CB accelerates a switch from TNFα, NKT-driven immune response toward an IFN-γ driven CD4+/CD8+ T cell response in MC38 tumors. These results uncover a novel NKT/T cell switch that may be a key feature of CB response in CD1d+ tumors.

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