Transcriptome Analysis of the Cecal Tonsil of Jingxing Yellow Chickens Revealed the Mechanism of Differential Resistance to Salmonella

Salmonella is one of the most common food-borne pathogens. It can be transmitted between chickens, as well as to people by contaminated poultry products. In our study, we distinguished chickens with different resistances mainly based on bacterial loads. We compared the cecal tonsil transcriptomes between the susceptible and resistant chickens after Salmonella infection, aiming to identify the crucial genes participating in the antibacterial activity in the cecal tonsil. A total of 3214 differentially expressed genes (DEGs), including 2092 upregulated and 1122 downregulated genes, were identified between the two groups (fold change ≥ 2.0, padj < 0.05). Many DEGs were mainly involved in the regulation of two biological processes: crosstalk between the cecal tonsil epithelium and pathogenic bacteria, such as focal adhesion, extracellular-matrix–receptor interaction, and regulation of the actin cytoskeleton and host immune response including the cytokine–receptor interaction. In particular, the challenged resistant birds exhibited strong activation of the intestinal immune network for IgA production, which perhaps contributed to the resistance to Salmonella infection. These findings give insight into the mRNA profile of the cecal tonsil between the two groups after initial Salmonella stimulation, which may extend the known complexity of molecular mechanisms in chicken immune response to Salmonella.

Download Full-text

Association of SPOP Expression with the Immune Response to Salmonella Infection in Chickens

Animals ◽

10.3390/ani10020307 ◽

2020 ◽

Vol 10 (2) ◽

pp. 307

Author(s):

Fei Wang ◽

Qinghe Li ◽

Qiao Wang ◽

Maiqing Zheng ◽

Jie Wen ◽

...

Keyword(s):

Immune Response ◽

Zinc Finger Protein ◽

Salmonella Infection ◽

Macrophage Cells ◽

Chicken Macrophage ◽

Polymerase Chain ◽

Iga Production ◽

Broad Complex

Salmonellosis is a zoonosis that is not only harmful to the health of poultry but also poses a threat to human health. Although many measures have been put in place to reduce morbidity, they have not provided satisfactory results. Therefore, it is necessary to clarify the immune mechanisms involved in improving the resistance of chickens against Salmonella. BTB (Broad-complex Tramtrack and Bric-a-brac) Speckle-type POZ (poxvirus and zinc finger) protein (SPOP) regulates protein expression by promoting substrate ubiquitination and degradation. The correlation between SPOP expression and the immune response has not been fully described. Therefore, the aim of this study was to clarify this relationship. In vitro, we stimulated chicken macrophage cells (HD11) with lipopolysaccharide, then analyzed the correlation between SPOP and IL1β or IL8 expression using quantitative real-time polymerase chain reaction (qRT-PCR). In vivo, we infected 7-days-old chickens with Salmonella Typhimurium, then analyzed the association between SPOP expression and the immune response, including IL1β and IL8 expression, IgA production, and bacterial loads. We found that SPOP may participate in the regulation of the immune response in macrophage cells. SPOP expression was negatively correlated with IL-1β and IL-8 expression both in vivo and in vitro. SPOP expression was also negatively related to bacterial loads and immunoglobulin (Ig) A production. These results indicate that SPOP may have important functions in the response to Salmonella infection.

Download Full-text

Type 1 piliated uropathogenic Escherichia coli hijack the host immune response by binding to CD14

10.1101/2021.10.18.464770 ◽

2021 ◽

Author(s):

Kathrin Tomasek ◽

Alexander Leithner ◽

Ivana Glatzova ◽

Michael Sebastian Lukesch ◽

Calin C Guet ◽

...

Keyword(s):

Escherichia Coli ◽

Immune Response ◽

T Cell Activation ◽

Bacterial Infections ◽

Pathogenic Bacteria ◽

Cell Activation ◽

Molecular Mechanisms ◽

Limiting Factors ◽

Tract Infections

A key attribute of persistent or recurring bacterial infections is the ability of the pathogen to evade the host’s immune response. Many Enterobacteriaceae express type 1 pili, a pre-adapted virulence trait, to invade host epithelial cells and establish persistent infections. However, the molecular mechanisms and strategies by which bacteria actively circumvent the immune response of the host remain poorly understood. Here, we identified CD14, the major co-receptor for lipopolysaccharide detection, on dendritic cells as a previously undescribed binding partner of FimH, the protein located at the tip of the type 1 pilus of Escherichia coli. The FimH amino acids involved in CD14 binding are highly conserved across pathogenic and non-pathogenic strains. Binding of pathogenic bacteria to CD14 lead to reduced dendritic cell migration and blunted expression of co-stimulatory molecules, both rate-limiting factors of T cell activation. While defining an active molecular mechanism of immune evasion by pathogens, the interaction between FimH and CD14 represents a potential target to interfere with persistent and recurrent infections, such as urinary tract infections or Crohn’s disease.

Download Full-text

Integrated Analysis of lncRNA and mRNA Transcriptomes Reveals New Regulators of Ubiquitination and the Immune Response in Silica-Induced Pulmonary Fibrosis

BioMed Research International ◽

10.1155/2019/6305065 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11

Author(s):

Yao Zhou ◽

Li He ◽

Xiao-Dan Liu ◽

Hua Guan ◽

Ying Li ◽

...

Keyword(s):

Immune Response ◽

Pulmonary Fibrosis ◽

Molecular Mechanisms ◽

Kegg Pathway ◽

Differentially Expressed ◽

Coexpression Network ◽

Receptor Interaction ◽

Integrated Analysis ◽

Biological Processes ◽

Biological Functions

Objectives. As an epigenetic player, long noncoding RNAs (LncRNAs) have been reported to participate in multiple biological processes; however, their biological functions in silica-induced pulmonary fibrosis (SIPF) occurrence and development remain incompletely understood.Methods. Five case/control pairs were used to perform integrated transcriptomes analysis of lncRNA and mRNA. Prediction of lncRNA and mRNA functions was aided by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Additionally, we constructed a coexpression network of lncRNAs and mRNAs to identify targets of regulation.Results. In total, 1069 differentially expressed mRNAs and 366 lncRNAs were identified with the changes more than 2 times (p<0.05), of which 351 downregulated mRNA and 31 downregulated lncRNA were <0.5 (p<0.05) and those of 718 upregulated mRNAs and 335 upregulated lncRNA were >2 (p<0.05). The levels of 10 lncRNAs were measured via qRT-PCR; the results were consistent with the microarray data. Four genes named of FEM1B, TRIM39, TRIM32, and KLHL15 were enriched significantly with ubiquitination and immune response. Cytokine-cytokine receptor interaction was the most significantly enriched KEGG pathway in both mRNAs and lncRNAs. The coexpression network revealed that a single lncRNA can interact with multiple mRNAs, and vice versa.Conclusions. lncRNA and mRNA expression were aberrant in patients with SIPF compared to controls, indicating that differentially expressed lncRNAs and mRNAs may play critical roles in SIPF development. Our study affords new insights into the molecular mechanisms of SIPF and identifies potential biomarkers and targets for SIPF diagnosis and treatment.

Download Full-text

Modulation of the Immune Response by Deferasirox in Myelodysplastic Syndrome Patients

Pharmaceuticals ◽

10.3390/ph14010041 ◽

2021 ◽

Vol 14 (1) ◽

pp. 41

Author(s):

Hana Votavova ◽

Zuzana Urbanova ◽

David Kundrat ◽

Michaela Dostalova Merkerova ◽

Martin Vostry ◽

...

Keyword(s):

Gene Expression ◽

Immune Response ◽

Blood Cell ◽

Myelodysplastic Syndrome ◽

Molecular Mechanisms ◽

Expression Profiles ◽

Adaptive Immune Response ◽

Gene Expression Profiles ◽

Iron Chelator ◽

Multiple Cancer

Deferasirox (DFX) is an oral iron chelator used to reduce iron overload (IO) caused by frequent blood cell transfusions in anemic myelodysplastic syndrome (MDS) patients. To study the molecular mechanisms by which DFX improves outcome in MDS, we analyzed the global gene expression in untreated MDS patients and those who were given DFX treatment. The gene expression profiles of bone marrow CD34+ cells were assessed by whole-genome microarrays. Initially, differentially expressed genes (DEGs) were determined between patients with normal ferritin levels and those with IO to address the effect of excessive iron on cellular pathways. These DEGs were annotated to Gene Ontology terms associated with cell cycle, apoptosis, adaptive immune response and protein folding and were enriched in cancer-related pathways. The deregulation of multiple cancer pathways in iron-overloaded patients suggests that IO is a cofactor favoring the progression of MDS. The DEGs between patients with IO and those treated with DFX were involved predominantly in biological processes related to the immune response and inflammation. These data indicate DFX modulates the immune response mainly via neutrophil-related genes. Suppression of negative regulators of blood cell differentiation essential for cell maturation and upregulation of heme metabolism observed in DFX-treated patients may contribute to the hematopoietic improvement.

Download Full-text

TAMI-07. THE IMMUNE MICROENVIRONMENT IN LOWER GRADE GLIOMAS

Neuro-Oncology ◽

10.1093/neuonc/noaa215.896 ◽

2020 ◽

Vol 22 (Supplement_2) ◽

pp. ii214-ii214

Author(s):

Anupam Kumar ◽

Katharine Chen ◽

Claudia Petritsch ◽

Theodore Nicolaides ◽

Mariarita Santi-Vicini ◽

...

Keyword(s):

Immune Response ◽

T Cells ◽

Cd8 T Cells ◽

Molecular Mechanisms ◽

T Regulatory Cells ◽

Immune Cell ◽

T Cell Response ◽

Cytotoxic T Cell ◽

Lower Grade ◽

Functional Relationships

Abstract The determinants of the tumor-associated immune response in brain tumors are poorly understood. Using tumor samples from two molecularly distinct subtypes of lower grade glioma, MAPK-driven glioma with biallelic inactivation of CDKN2A (n=30) and IDH-mutant, 1p/19q-intact astrocytoma (n=29), we demonstrate qualitative and quantitative differences in the tumor-associated immune response and we investigate the molecular mechanisms involved. Histologically the MAPK-driven gliomas were comprised of pleomorphic xanthoastrocytoma (PXA) (n=11) and anaplastic PXA (n=19). Seven patients had paired samples from two sequential surgeries. Immune cell populations and their activity were determined by quantitative multiplex immunostaining and Digital Spatial Profiling and gene expression was analyzed by Nanostring. Functional studies were performed using established cell lines and two new patient-derived lines from MAPK-driven LGGs. MAPK-driven tumors exhibited an increased number of CD8+ T cells and tumor-associated microglial/macrophage (TAMs), including CD163+ TAMs, as compared to IDH-mutant astrocytoma. In contrast, IDH-mutant tumors had increased FOXP3+ immunosuppressive T regulatory cells. Transcriptional and protein level analyses in MAPK-driven tumors suggested an active cytotoxic T cell response with robust expression of granzyme B, present on 27% of CD8+ T cells, increased MHC class I expression, and altered cytokine profiles. Interestingly, MAPK-driven tumors also had increased expression of immunosuppressive molecules, including CXCR4, PD-L1, and VEGFA. Expression differences for cell surface and secreted proteins were confirmed in patient-derived tumor lines and functional relationships between altered chemokine expression and immune cell infiltration was investigated. Our data provide novel insights into the immune contexture of MAPK driven LGGs and suggest MAPK driven gliomas with biallelic inactivation of CDKN2A may be particularly vulnerable to immunotherapeutic modulation

Download Full-text

Cross-kingdom inhibition of bacterial virulence and communication by probiotic yeast metabolites

Microbiome ◽

10.1186/s40168-021-01027-8 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Orit Malka ◽

Dorin Kalson ◽

Karin Yaniv ◽

Reut Shafir ◽

Manikandan Rajendran ◽

...

Keyword(s):

Quorum Sensing ◽

Gut Microbiome ◽

Bacterial Infections ◽

Pathogenic Bacteria ◽

Molecular Mechanisms ◽

Human Microbiome ◽

Cell Communication ◽

Probiotic Yeast ◽

Gut Pathogen ◽

Cell Cell

Abstract Background Probiotic milk-fermented microorganism mixtures (e.g., yogurt, kefir) are perceived as contributing to human health, and possibly capable of protecting against bacterial infections. Co-existence of probiotic microorganisms are likely maintained via complex biomolecular mechanisms, secreted metabolites mediating cell-cell communication, and other yet-unknown biochemical pathways. In particular, deciphering molecular mechanisms by which probiotic microorganisms inhibit proliferation of pathogenic bacteria would be highly important for understanding both the potential benefits of probiotic foods as well as maintenance of healthy gut microbiome. Results The microbiome of a unique milk-fermented microorganism mixture was determined, revealing a predominance of the fungus Kluyveromyces marxianus. We further identified a new fungus-secreted metabolite—tryptophol acetate—which inhibits bacterial communication and virulence. We discovered that tryptophol acetate blocks quorum sensing (QS) of several Gram-negative bacteria, particularly Vibrio cholerae, a prominent gut pathogen. Notably, this is the first report of tryptophol acetate production by a yeast and role of the molecule as a signaling agent. Furthermore, mechanisms underscoring the anti-QS and anti-virulence activities of tryptophol acetate were elucidated, specifically down- or upregulation of distinct genes associated with V. cholerae QS and virulence pathways. Conclusions This study illuminates a yet-unrecognized mechanism for cross-kingdom inhibition of pathogenic bacteria cell-cell communication in a probiotic microorganism mixture. A newly identified fungus-secreted molecule—tryptophol acetate—was shown to disrupt quorum sensing pathways of the human gut pathogen V. cholerae. Cross-kingdom interference in quorum sensing may play important roles in enabling microorganism co-existence in multi-population environments, such as probiotic foods and the gut microbiome. This discovery may account for anti-virulence properties of the human microbiome and could aid elucidating health benefits of probiotic products against bacterially associated diseases.

Download Full-text

Integrated Insight into the Molecular Mechanisms of Spontaneous Abortion during Early Pregnancy in Pigs

International Journal of Molecular Sciences ◽

10.3390/ijms22126644 ◽

2021 ◽

Vol 22 (12) ◽

pp. 6644

Author(s):

Xupeng Zang ◽

Ting Gu ◽

Wenjing Wang ◽

Chen Zhou ◽

Yue Ding ◽

...

Keyword(s):

Immune Response ◽

Spontaneous Abortion ◽

Molecular Mechanisms ◽

Gene Set Enrichment Analysis ◽

Differentially Expressed ◽

Gene Set ◽

Cerna Network ◽

Major Interest ◽

End Stage ◽

Insight Into

Due to the high rate of spontaneous abortion (SAB) in porcine pregnancy, there is a major interest and concern on commercial pig farming worldwide. Whereas the perturbed immune response at the maternal–fetal interface is an important mechanism associated with the spontaneous embryo loss in the early stages of implantation in porcine, data on the specific regulatory mechanism of the SAB at the end stage of the implantation remains scant. Therefore, we used high-throughput sequencing and bioinformatics tools to analyze the healthy and arresting endometrium on day 28 of pregnancy. We identified 639 differentially expressed lncRNAs (DELs) and 2357 differentially expressed genes (DEGs) at the end stage of implantation, and qRT-PCR was used to verify the sequencing data. Gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and immunohistochemistry analysis demonstrated weaker immune response activities in the arresting endometrium compared to the healthy one. Using the lasso regression analysis, we screened the DELs and constructed an immunological competitive endogenous RNA (ceRNA) network related to SAB, including 4 lncRNAs, 11 miRNAs, and 13 genes. In addition, Blast analysis showed the applicability of the constructed ceRNA network in different species, and subsequently determined HOXA-AS2 in pigs. Our study, for the first time, demonstrated that the SAB events at the end stages of implantation is associated with the regulation of immunobiological processes, and a specific molecular regulatory network was obtained. These novel findings may provide new insight into the possibility of increasing the litter size of sows, making pig breeding better and thus improving the efficiency of animal husbandry production.

Download Full-text

Isolation and Characterization of Bacteriophage ZCSE6 against Salmonella spp.: Phage Application in Milk

Biologics ◽

10.3390/biologics1020010 ◽

2021 ◽

Vol 1 (2) ◽

pp. 164-176

Author(s):

Abdallah S. Abdelsattar ◽

Anan Safwat ◽

Rana Nofal ◽

Amera Elsayed ◽

Salsabil Makky ◽

...

Keyword(s):

Pathogenic Bacteria ◽

Raw Milk ◽

Salmonella Spp ◽

Isolation And Characterization ◽

Food Borne ◽

Wide Range ◽

Almost All ◽

And Control ◽

Milk And Dairy Products

Food safety is very important in the food industry as most pathogenic bacteria can cause food-borne diseases and negatively affect public health. In the milk industry, contamination with Salmonella has always been a challenge, but the risks have dramatically increased as almost all bacteria now show resistance to a wide range of commercial antibiotics. This study aimed to isolate a bacteriophage to be used as a bactericidal agent against Salmonella in milk and dairy products. Here, phage ZCSE6 has been isolated from raw milk sample sand molecularly and chemically characterized. At different multiplicities of infection (MOIs) of 0.1, 0.01, and 0.001, the phage–Salmonella interaction was studied for 6 h at 37 °C and 24 h at 8 °C. In addition, ZCSE6 was tested against Salmonella contamination in milk to examine its lytic activity for 3 h at 37 °C. The results showed that ZCSE6 has a small genome size (<48.5 kbp) and belongs to the Siphovirus family. Phage ZCSE6 revealed a high thermal and pH stability at various conditions that mimic milk manufacturing and supply chain conditions. It also demonstrated a significant reduction in Salmonella concentration in media at various MOIs, with higher bacterial eradication at higher MOI. Moreover, it significantly reduced Salmonella growth (MOI 1) in milk, manifesting a 1000-fold decrease in bacteria concentration following 3 h incubation at 37 °C. The results highlighted the strong ability of ZCSE6 to kill Salmonella and control its growth in milk. Thus, ZCSE6 is recommended as a biocontrol agent in milk to limit bacterial growth and increase the milk shelf-life.

Download Full-text

DAP12 Inhibits Pulmonary Immune Responses to Cryptococcus neoformans

Infection and Immunity ◽

10.1128/iai.00222-16 ◽

2016 ◽

Vol 84 (6) ◽

pp. 1879-1886 ◽

Cited By ~ 5

Author(s):

Lena J. Heung ◽

Tobias M. Hohl

Keyword(s):

Immune Response ◽

Nk Cells ◽

Cryptococcus Neoformans ◽

Molecular Mechanisms ◽

Content Type ◽

Effector Cells ◽

Opportunistic Fungal Pathogen ◽

Efficient Uptake ◽

Bacteria And Fungi

Cryptococcus neoformansis an opportunistic fungal pathogen that is inhaled into the lungs and can lead to life-threatening meningoencephalitis in immunocompromised patients. Currently, the molecular mechanisms that regulate the mammalian immune response to respiratory cryptococcal challenge remain poorly defined. DAP12, a signaling adapter for multiple pattern recognition receptors in myeloid and natural killer (NK) cells, has been shown to play both activating and inhibitory roles during lung infections by different bacteria and fungi. In this study, we demonstrate that DAP12 plays an important inhibitory role in the immune response toC. neoformans. Infectious outcomes in DAP12−/−mice, including survival and lung fungal burden, are significantly improved compared to those in C57BL/6 wild-type (WT) mice. We find that eosinophils and macrophages are decreased while NK cells are increased in the lungs of infected DAP12−/−mice. In contrast to WT NK cells, DAP12−/−NK cells are able to repressC. neoformansgrowthin vitro. Additionally, DAP12−/−macrophages are more highly activated than WT macrophages, with increased production of tumor necrosis factor (TNF) and CCL5/RANTES and more efficient uptake and killing ofC. neoformans. These findings suggest that DAP12 acts as a brake on the pulmonary immune response toC. neoformansby promoting pulmonary eosinophilia and by inhibiting the activation and antifungal activities of effector cells, including NK cells and macrophages.

Download Full-text

Identification of Differentially Expressed Genes in Porcine Ovaries at Proestrus and Estrus Stages Using RNA-Seq Technique

BioMed Research International ◽

10.1155/2018/9150723 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 2

Author(s):

Songbai Yang ◽

Xiaolong Zhou ◽

Yue Pei ◽

Han Wang ◽

Ke He ◽

...

Keyword(s):

Differentially Expressed Genes ◽

Molecular Mechanisms ◽

Expression Patterns ◽

Hormone Secretion ◽

Differentially Expressed ◽

Receptor Interaction ◽

The Novel ◽

Kegg Pathways ◽

Go Enrichment ◽

Single Organism

Estrus is an important factor for the fecundity of sows, and it is involved in ovulation and hormone secretion in ovaries. To better understand the molecular mechanisms of porcine estrus, the expression patterns of ovarian mRNA at proestrus and estrus stages were analyzed using RNA sequencing technology. A total of 2,167 differentially expressed genes (DEGs) were identified (P≤0.05, log2 Ratio≥1), of which 784 were upregulated and 1,383 were downregulated in the estrus compared with the proestrus group. Gene Ontology (GO) enrichment indicated that these DEGs were mainly involved in the cellular process, single-organism process, cell and cell part, and binding and metabolic process. In addition, a pathway analysis showed that these DEGs were significantly enriched in 33 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, including cell adhesion molecules, ECM-receptor interaction, and cytokine-cytokine receptor interaction. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) confirmed the differential expression of 10 selected DEGs. Many of the novel candidate genes identified in this study will be valuable for understanding the molecular mechanisms of the sow estrous cycle.

Download Full-text