Modulation Of Host Response Research Articles

Impact of Senolytic Treatment on Gene Expression in Aged Lung.

Cellular senescence plays a key role in mediating tissue remodeling and modulation of host responses to pathogenic stimuli. Our current study was designed to gain a better understanding of the impact of short-term senolytic treatment or inflammatory stimulation on lung senescence. The results of our study demonstrate that short term treatment of aged adult mice (20 months of age) with senolytics, quercetin, and dasatinib decreases p16 and p21 expression in lung tissue. Short-term treatment with senolytics also significantly improved the expression of genes associated with genomic instability, telomere attrition, mitochondrial dysfunction, DNA binding, and the inflammatory response. In contrast, in response to low-dose LPS administration, there was increased expression of genes associated with genomic instability, mitochondrial dysfunction, and heightened inflammatory responses in young adult murine lung (3 months of age). Taken together, the results of our current study illustrate the efficacy of senolytic treatment on modulating responses in aged lung and the potential role of chronic low dose inflammation on senescence induction in the lung.

Generation and Functional Analysis of Defective Viral Genomes during SARS-CoV-2 Infection.

Defective viral genomes (DVGs) have been identified in many RNA viruses as a major factor influencing antiviral immune response and viral pathogenesis. However, the generation and function of DVGs in SARS-CoV-2 infection are less known. In this study, we elucidated DVG generation in SARS-CoV-2 and its relationship with host antiviral immune response. We observed DVGs ubiquitously from transcriptome sequencing (RNA-seq) data sets of in vitro infections and autopsy lung tissues of COVID-19 patients. Four genomic hot spots were identified for DVG recombination, and RNA secondary structures were suggested to mediate DVG formation. Functionally, bulk and single-cell RNA-seq analysis indicated the interferon (IFN) stimulation of SARS-CoV-2 DVGs. We further applied our criteria to the next-generation sequencing (NGS) data set from a published cohort study and observed a significantly higher amount and frequency of DVG in symptomatic patients than those in asymptomatic patients. Finally, we observed exceptionally diverse DVG populations in one immunosuppressive patient up to 140 days after the first positive test of COVID-19, suggesting for the first time an association between DVGs and persistent viral infections in SARS-CoV-2. Together, our findings strongly suggest a critical role of DVGs in modulating host IFN responses and symptom development, calling for further inquiry into the mechanisms of DVG generation and into how DVGs modulate host responses and infection outcome during SARS-CoV-2 infection. IMPORTANCE Defective viral genomes (DVGs) are generated ubiquitously in many RNA viruses, including SARS-CoV-2. Their interference activity to full-length viruses and IFN stimulation provide the potential for them to be used in novel antiviral therapies and vaccine development. SARS-CoV-2 DVGs are generated through the recombination of two discontinuous genomic fragments by viral polymerase complex, and this recombination is also one of the major mechanisms for the emergence of new coronaviruses. Focusing on the generation and function of SARS-CoV-2 DVGs, these studies identify new hot spots for nonhomologous recombination and strongly suggest that the secondary structures within viral genomes mediate the recombination. Furthermore, these studies provide the first evidence for IFN stimulation activity of de novo DVGs during natural SARS-CoV-2 infection. These findings set up the foundation for further mechanism studies of SARS-CoV-2 recombination and provide evidence to harness the immunostimulatory potential of DVGs in the development of a vaccine and antivirals for SARS-CoV-2.

Interferons and Resistance Mechanisms in Tumors and Pathogen-Driven Diseases-Focus on the Major Histocompatibility Complex (MHC) Antigen Processing Pathway.

Interferons (IFNs), divided into type I, type II, and type III IFNs represent proteins that are secreted from cells in response to various stimuli and provide important information for understanding the evolution, structure, and function of the immune system, as well as the signaling pathways of other cytokines and their receptors. They exert comparable, but also distinct physiologic and pathophysiologic activities accompanied by pleiotropic effects, such as the modulation of host responses against bacterial and viral infections, tumor surveillance, innate and adaptive immune responses. IFNs were the first cytokines used for the treatment of tumor patients including hairy leukemia, renal cell carcinoma, and melanoma. However, tumor cells often develop a transient or permanent resistance to IFNs, which has been linked to the escape of tumor cells and unresponsiveness to immunotherapies. In addition, loss-of-function mutations in IFN signaling components have been associated with susceptibility to infectious diseases, such as COVID-19 and mycobacterial infections. In this review, we summarize general features of the three IFN families and their function, the expression and activity of the different IFN signal transduction pathways, and their role in tumor immune evasion and pathogen clearance, with links to alterations in the major histocompatibility complex (MHC) class I and II antigen processing machinery (APM). In addition, we discuss insights regarding the clinical applications of IFNs alone or in combination with other therapeutic options including immunotherapies as well as strategies reversing the deficient IFN signaling. Therefore, this review provides an overview on the function and clinical relevance of the different IFN family members, with a specific focus on the MHC pathways in cancers and infections and their contribution to immune escape of tumors.

Antifungal Activity and Effect of Plant-Associated Bacteria on Phenolic Synthesis of Quercus robur L.

Europe's forests, particularly in Ukraine, are highly vulnerable to climate change. The maintenance and improvement of forest health are high-priority issues, and various stakeholders have shown an interest in understanding and utilizing ecological interactions between trees and their associated microorganisms. Endophyte microbes can influence the health of trees either by directly interacting with the damaging agents or modulating host responses to infection. In the framework of this work, ten morphotypes of endophytic bacteria from the tissues of unripe acorns of Quercus robur L. were isolated. Based on the results of the sequenced 16S rRNA genes, four species of endophytic bacteria were identified: Bacillus amyloliquefaciens, Bacillus subtilis, Delftia acidovorans, and Lelliottia amnigena. Determining the activity of pectolytic enzymes showed that the isolates B. subtilis and B. amyloliquefaciens could not cause maceration of plant tissues. Screening for these isolates revealed their fungistatic effect against phytopathogenic micromycetes, namely Fusarium tricinctum, Botrytis cinerea, and Sclerotinia sclerotiorum. Inoculation of B. subtilis, B. amyloliquefaciens, and their complex in oak leaves, in contrast to phytopathogenic bacteria, contributed to the complete restoration of the epidermis at the sites of damage. The phytopathogenic bacteria Pectobacterium and Pseudomonas caused a 2.0 and 2.2 times increase in polyphenol concentration in the plants, respectively, while the ratio of antioxidant activity to total phenolic content decreased. Inoculation of Bacillus amyloliquefaciens and Bacillus subtilis isolates into oak leaf tissue were accompanied by a decrease in the total pool of phenolic compounds. The ratio of antioxidant activity to total phenolic content increased. This indicates a qualitative improvement in the overall balance of the oak leaf antioxidant system induced by potential PGPB. Thus, endophytic bacteria of the genus Bacillus isolated from the internal tissues of unripe oak acorns have the ability of growth biocontrol and spread of phytopathogens, indicating their promise for use as biopesticides.

Oral intake of heat-killed Lactiplantibacillus pentosus ONRICb0240 partially protects mice against SARS-CoV-2 infection

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the ongoing coronavirus pandemic. Besides vaccines and antiviral drugs, probiotics have attracted attention for prevention of SARS-CoV-2 infection. Here, we examined the efficacy of heat-killed Lactiplantibacillus pentosus ONRICb0240 (b240) against SARS-CoV-2 infection in mice. We observed that oral intake of heat-killed b240 did not affect virus titers in the respiratory organs of SARS-CoV-2-infected mice, but did provide partial protection against SARS-CoV-2 infection. In addition, heat-killed b240 treatment suppressed the expression of IL-6, a key proinflammatory cytokine, on Day 2 post-infection. Our results highlight the promising protective role of heat-killed b240 and suggest a possible mechanism by which heat-killed b240 partially protects against SARS-CoV-2 infection by modulating host responses.

A Balance between Pro-Inflammatory and Pro-Reparative Macrophages is Observed in Regenerative D-MAPS.

Microporous annealed particle scaffolds (MAPS) are a new class of granular materials generated through the interlinking of tunable microgels, which produce an interconnected network of void space. These microgel building blocks can be designed with different mechanical or bio-active parameters to facilitate cell infiltration and modulate host response. Previously, changing the chirality of the microgel crosslinking peptides from L- to D-amino acids led to significant tissue regeneration and functional recovery in D-MAPS-treated cutaneous wounds. In this study, the immunomodulatory effect of D-MAPS in a subcutaneous implantation model is investigated. How macrophages are the key antigen-presenting cells to uptake and present these biomaterials to the adaptive immune systemisuncovered. A robust linker-specific IgG2b/IgG1 response to D-MAPS is detected as early as 14 days post-implantation. The fine balance between pro-regenerative and pro-inflammatory macrophage phenotypes is observed in D-MAPS as an indicator for regenerative scaffolds. The work offers valuable insights into the temporal cellular response to synthetic porous scaffolds and establishes a foundation for further optimization of immunomodulatory pro-regenerative outcomes.

Vitamin D (1α,25(OH)2D3) supplementation minimized multinucleated giant cells formation and inflammatory response during Burkholderia pseudomallei infection in human lung epithelial cells.

Melioidosis is an infectious disease with high mortality rates in human, caused by the bacterium Burkholderia pseudomallei. As an intracellular pathogen, B. pseudomallei can escape from the phagosome and induce multinucleated giant cells (MNGCs) formation resulting in antibiotic resistance and immune evasion. A novel strategy to modulate host response against B. pseudomallei pathogenesis is required. In this study, an active metabolite of vitamin D3 (1α,25-dihydroxyvitamin D3 or 1α,25(OH)2D3) was selected to interrupt pathogenesis of B. pseudomallei in a human lung epithelium cell line, A549. The results demonstrated that pretreatment with 10-6 M 1α,25(OH)2D3 could reduce B. pseudomallei internalization to A549 cells at 4 h post infection (P < 0.05). Interestingly, the presence of 1α,25(OH)2D3 gradually reduced MNGC formation at 8, 10 and 12 h compared to that of the untreated cells (P < 0.05). Furthermore, pretreatment with 10-6 M 1α,25(OH)2D3 considerably increased hCAP-18/LL-37 mRNA expression (P < 0.001). Additionally, pro-inflammatory cytokines, including MIF, PAI-1, IL-18, CXCL1, CXCL12 and IL-8, were statistically decreased (P < 0.05) in 10-6 M 1α,25(OH)2D3-pretreated A549 cells by 12 h post-infection. Taken together, this study indicates that pretreatment with 10-6 M 1α,25(OH)2D3 has the potential to reduce the internalization of B. pseudomallei into host cells, decrease MNGC formation and modulate host response during B. pseudomallei infection by minimizing the excessive inflammatory response. Therefore, 1α,25(OH)2D3 supplement may provide an effective supportive treatment for melioidosis patients to combat B. pseudomallei infection and reduce inflammation in these patients.

A mechanism for transcriptional regulation of innate immune response genes by RSV NS1 protein.

Human Respiratory syncytial virus (RSV) is a main cause of bronchiolitis in young children and a still unmet target for pediatric vaccines and antiviral drugs. RSV has evolved a unique strategy to evade host immune response by coding for two non-structural proteins NS1 and NS2, identified as interferon antagonists. Recently it was suggested that NS1 modulates host gene transcription via interactions with chromatin and the Mediator complex. Moreover, the C-terminal RSV NS1 α-helix, α3, was reported to be involved in modulation of host response and gene expression. Here, after identifying the MED25 Mediator subunit as an NS1 interactor in a yeast two-hybrid screen, we demonstrated that NS1 directly interacts with MED25 in cells and in vitro. We assigned this interaction to the MED25-ACID domain, a target of viral transcriptional activators, such as Herpes simplex virus VP16. We showed that NS1 α3 primarily targets the VP16 transactivation domain (TAD) binding site of MED25-ACID. In particular, we found out that NS1 could compete with the TAD of ATF6α, a master regulator of ER stress response activated upon viral infection, for MED25-ACID binding. The affinity for MED25-ACID determined using an NS1-α3 peptide was surprisingly low, as compared to that of full-length NS1. Although this can be partly explained by the unfolded state of the isolated peptide, it suggests the presence of a second binding site. We indeed observed that the NS1Δα3 deletion mutant was able to bind to MED25-ACID. Altogether our findings suggest a mechanism for transcription modulation of specific genes by RSV NS1, and hence for modulation of the host immune response, where NS1 competes with cellular TADs for recruitment of the Mediator MED25 subunit.

Peptidoglycan enzymes of Francisella: Roles in cell morphology and pathogenesis, and potential as therapeutic targets.

Peptidoglycan, found within the cell wall of bacteria, is a structure critical for maintaining cell morphology and providing a protective barrier in diverse environments. Peptidoglycan is a remarkably dynamic structure that is constantly remodeled during cell growth and division by various peptidoglycan enzymes. Numerous peptidoglycan enzymes have been characterized from diverse bacteria and are highly sought after as targets for therapeutics. However, very little is known about these enzymes within the biothreat agent Francisella tularensis. As the causative agent of tularemia, F. tularensis is classified as a category A biothreat pathogen, in part due to its low infectious dose and lack of FDA-approved vaccine. Many bacterial species encode multiple peptidoglycan enzymes with redundant functions that allow for compensation if one of the enzymes are inactivated. In contrast, F. tularensis appears to lack this redundancy, indicating peptidoglycan enzymes may be completely essential for growth and could be exploited as targets for medical countermeasures. Indeed, several peptidoglycan enzymes in F. tularensis have been shown to play important roles in cell division, cell morphology, virulence, and modulation of host response. The aim of this review is to summarize findings from the current literature on peptidoglycan enzymes present in Francisella and discuss areas where future research efforts might be directed. We conclude that Francisella harbors a distinct set of peptidoglycan enzymes important for cell growth and virulence and represent potentially valuable targets for the development of novel therapeutics.

Mediterranean diet component oleic acid increases protective lipid mediators and improves trabecular bone in a Porphyromonas gingivalis inoculation model.

Therapeutic modulation of bacterial-induced inflammatory host response is being investigated in gingival inflammation and periodontal disease pathology. Therefore, dietary intake of the monounsaturated fatty acid (FA) oleic acid (OA (C18:1)), which is the main component of Mediterranean-style diets, and saturated FA palmitic acid (PA (C16:0)), which is a component of Western-style diets, was investigated for their modifying potential in an oral inoculation model of Porphyromonas gingivalis. Normal-weight C57BL/6-mice received OA- or PA-enriched diets (PA-ED, OA-ED, PA/OA-ED) or normal standard diet for 16 weeks and were inoculated with P. gingivalis/placebo (n=12/group). Gingival inflammation, alveolar bone structure, circulating lipid mediators, and in vitro cellular response were determined. FA treatment of P. gingivalis-lipopolysaccharide-incubated gingival fibroblasts (GFbs) modified inflammatory activation, which only PA exacerbated with concomitant TNF-α stimulation. Mice exhibited no signs of acute inflammation in gingiva or serum and no inoculation- or nutrition-associated changes of the crestal alveolar bone. However, following P. gingivalis inoculation, OA-ED improved oral trabecular bone micro-architecture and enhanced circulating pro-resolving mediators resolvin D4 (RvD4) and 4-hydroxydocosahexaenoic acid (4-HDHA), whereas PA-ED did not. In vitro experiments demonstrated significantly improved differentiation in RvD4- and 4-HDHA-treated primary osteoblast cultures and reduced the expression of osteoclastogenic factors in GF. Further, P. gingivalis infection of OA-ED animals led to a serum composition that suppressed osteoclastic differentiation in vitro. Our results underline the preventive impact of Mediterranean-style OA-EDs by indicating their pro-resolving nature beyond anti-inflammatory properties.

Elucidating host cell response pathways and repurposing therapeutics for SARS-CoV-2 and other coronaviruses

COVID-19, first reported in late 2019, is an ongoing pandemic that has been causing devastation across the globe. Although there are multiple vaccines that can prevent severe symptoms, effective COVID-19 therapeutics are still of importance. Using our proprietary in silico engine, we screened more than 22,000 unique compounds represented by over half a million gene expression profiles to uncover compounds that can be repurposed for SARS-CoV-2 and other coronaviruses in a timely and cost-efficient manner. We then tested 13 compounds in vitro and found three with potency against SARS-CoV-2 with reasonable cytotoxicity. Bortezomib and homoharringtonine are some of the most promising hits with IC50 of 1.39 μM and 0.16 μM, respectively for SARS-CoV-2. Tanespimycin and homoharringtonine were effective against the common cold coronaviruses. In-depth analysis highlighted proteasome, ribosome, and heat shock pathways as key targets in modulating host responses during viral infection. Further studies of these pathways and compounds have provided novel and impactful insights into SARS-CoV-2 biology and host responses that could be further leveraged for COVID-19 therapeutics development.

A multifunctional drug consisting of tetracycline conjugated with odanacatib for efficient periodontitis therapy.

The treatment of periodontitis can be very challenging due to its complex etiologies. A new pharmacologic strategy entitled "host-modulation therapy," has been introduced to improve periodontal treatment outcomes. Supposedly, a multifunctional drug with the potential for bacterial infection prevention, host-response modulation and bone healing promotion would be a promising option for periodontitis therapy, but related studies remain substantially lacking. In this study, we successfully conjugated tetracycline with odanacatib (a selective inhibitor of cathepsin K) to construct a multifunctional drug (TC-ODN). We discovered that TC-ODN could promote macrophages polarizing toward anti-inflammatory phenotype and promote osteogenesis of PDLSCs under inflammatory microenvironment. In vivo, TC-ODN could be absorbed and distributed specifically to the bone after systemic administration, and accumulation of TC-ODN increased bone mineral density in ovariectomized rats. Importantly, periodontal administration of TC-ODN could successfully promote bone healing in periodontitis rats with alveolar bone loss. The findings in our study uncovered the excellent biocompatibility and multifunction of TC-ODN, including bone-targeted accumulation, immunoregulation, anti-inflammatory activity and promotion of bone healing, which might contribute to the clinical treatment of periodontitis.

Modulation of host response - use in periodontal diseases

Modulation of host response - use in periodontal diseases

Human Milk Oligosaccharide 2'-Fucosyllactose Modulates Local Viral Immune Defense by Supporting the Regulatory Functions of Intestinal Epithelial and Immune Cells.

Human milk contains bioactive components that provide protection against viral infections in early life. In particular, intestinal epithelial cells (IEC) have key regulatory roles in the prevention of enteric viral infections. Here we established an in vitro model to study the modulation of host responses against enteric viruses mimicked by poly I:C (pIC). The effects of 2′-fucosyllactose (2′FL), abundantly present in human milk, were studied on IEC and/or innate immune cells, and the subsequent functional response of the adaptive immune cells. IEC were pre-incubated with 2′FL and stimulated with naked or Lyovec™-complexed pIC (LV-pIC). Additionally, monocyte-derived dendritic cells (moDC) alone or in co-culture with IEC were stimulated with LV-pIC. Then, conditioned-moDC were co-cultured with naïve CD4+ T helper (Th)-cells. IEC stimulation with naked or LV-pIC promoted pro-inflammatory IL-8, CCL20, GROα and CXCL10 cytokine secretion. However, only exposure to LV-pIC additionally induced IFNβ, IFNλ1 and CCL5 secretion. Pre-incubation with 2′FL further increased pIC induced CCL20 secretion and LV-pIC induced CXCL10 secretion. LV-pIC-exposed IEC/moDC and moDC cultures showed increased secretion of IL-8, GROα, IFNλ1 and CXCL10, and in the presence of 2′FL galectin-4 and -9 were increased. The LV-pIC-exposed moDC showed a more pronounced secretion of CCL20, CXCL10 and CCL5. The moDC from IEC/moDC cultures did not drive T-cell development in moDC/T-cell cultures, while moDC directly exposed to LV-pIC secreted Th1 driving IL-12p70 and promoted IFNγ secretion by Th-cells. Hereby, a novel intestinal model was established to study mucosal host-defense upon a viral trigger. IEC may support intestinal homeostasis, regulating local viral defense which may be modulated by 2′FL. These results provide insights regarding the protective capacity of human milk components in early life.

A filarial parasite-encoded human IL-10 receptor antagonist reveals a novel strategy to modulate host responses.

Interleukin (IL)-10 is the primary cytokine driving the modulation of the host response in filarial infections. We performed binding assays with Brugia malayi antigen extracts and human IL-10R1. Bm5539 was the top-binding hit. We identified a short sequence, termed truncated Bm5339, that has structural similarities to the human IL-10 functional dimer. Sequence comparisons revealed that other filarial parasites possess Bm5539 orthologues. Using recombinant Bm5539 in a modified Luciferase Immunoprecipitation System assay, we confirmed that both the truncated and full-length forms of the protein can bind to human IL-10R1. Truncated Bm5539 could inhibit human IL-10-driven phosphorylation of STAT3, thereby demonstrating that Bm5539 acts as an IL-10 antagonist, most likely through competitive binding to the receptor. We provide a structural basis for these observations using computational modeling and simulations. This parasite-encoded cytokine receptor antagonist provides an additional lens through which parasite-induced modulation of the host immune response can be examined.

Host Response Modulation Therapy in the Diabetes Mellitus-Periodontitis Conjuncture: A Narrative Review.

The inflammatory response of the host in periodontitis is the phenomenon that underlies the onset and evolution of periodontal destructive phenomena. A number of systemic factors, such as diabetes mellitus (DM), can negatively affect the patient with periodontitis, just as the periodontal disease can aggravate the status of the DM patient. Host response modulation therapy involves the use of anti-inflammatory and anti-oxidant products aimed at resolving inflammation, stopping destructive processes, and promoting periodontal healing, all important aspects in patients with high tissue loss rates, such as diabetic patients. This paper reviews the data available in the literature on the relationship between DM and periodontitis, the main substances modulating the inflammatory response (nonsteroidal anti-inflammatory drugs, sub-antimicrobial doses of doxycycline, or omega-3 fatty acids and their products, specialized pro-resolving mediators), as well as their application in diabetic patients.

Bacterial extracellular vesicles control murine norovirus infection through modulation of antiviral immune responses.

Human norovirus is the primary cause of non-bacterial gastroenteritis globally and is the second leading cause of diarrheal deaths in children in developing countries. However, effective therapeutics which prevent or clear norovirus infection are not yet available due to a lack of understanding regarding norovirus pathogenesis. Evidence shows that noroviruses can bind to the surface of commensal bacteria, and the presence of these bacteria alters both acute and persistent murine norovirus infection through the modulation of host immune responses. Interestingly, norovirus-bacterial interactions also affect the bacteria by inducing bacterial stress responses and increasing the production of bacterial extracellular vesicles. Given the established ability of these vesicles to easily cross the intestinal barriers, enter the lamina propria, and modulate host responses, we hypothesized that bacterial extracellular vesicles influence murine norovirus infection through modulation of the antiviral immune response. In this study, we show that murine norovirus can attach to purified bacterial vesicles, facilitating co-inoculation of target cells with both virus and vesicle. Furthermore, we have found that when murine noroviruses and vesicles are used to co-inoculate macrophages, viral infection is reduced compared to virus infection alone. Specifically, co-inoculation with bacterial vesicles results in higher production and release of pro-inflammatory cytokines in response to viral infection. Ultimately, given that murine norovirus infection increases bacterial vesicle production in vivo, these data indicate that bacterial vesicles may serve as a mechanism by which murine norovirus infection is ultimately controlled and limited to a short-term disease.

Vitamin D boosts immune response of macrophages through a regulatory network of microRNAs and mRNAs

Vitamin D is associated with the stimulation of innate immunity, inflammation, and host defense against pathogens. Macrophages express receptors of Vitamin D, regulating the transcription of genes related to immune processes. However, the transcriptional and post-transcriptional strategies controlling gene expression in differentiated macrophages, and how they are influenced by Vitamin D are not well understood. We studied whether Vitamin D enhances immune response by regulating the expression of microRNAs and mRNAs. Analysis of the transcriptome showed differences in expression of 199 genes, of which 68% were up-regulated, revealing the cell state of monocyte-derived macrophages differentiated with Vitamin D (D3-MDMs) as compared to monocyte-derived macrophages (MDMs). The differentially expressed genes appear to be associated with pathophysiological processes, including inflammatory responses, and cellular stress. Transcriptional motifs in promoter regions of up- or down-regulated genes showed enrichment of VDR motifs, suggesting possible roles of transcriptional activator or repressor in gene expression. Further, the microRNA-Seq analysis indicated that there were 17 differentially expressed miRNAs, of which, seven were up-regulated and 10 down-regulated, suggesting that Vitamin D plays a critical role in the regulation of miRNA expression during macrophages differentiation. The miR-6501-3p, miR-1273h-5p, miR-665, miR-1972, miR-1183, miR-619-5p were down-regulated in D3-MDMs compared to MDMs. The integrative analysis of miRNA and mRNA expression profiles predicts that miR-1972, miR-1273h-5p, and miR-665 regulate genes PDCD1LG2, IL-1B, and CD274, which are related to the inflammatory response. Results suggest an essential role of Vitamin D in macrophage differentiation that modulates host response against pathogens, inflammation, and cellular stress.

Uses of Plant Growth Regulators and Biofertilizers in Fruit Crops: A Review

Plant growth regulators are extremely important natural hormones which control the growth and the physiological factors within the plant. They are naturally occurring as well as synthetic. PGRs like Auxins, ethylene, cytokinins and gibberellins are the growth inhibitors and growth retardants. The foliar application of plant growth regulators helped in increasing the quality of the fruit crops. Auxin is required for fruit retention in sweet cherry, litchi, grapevine, snake fruit and tomato. Most commonly used auxins are IBA, NAA, IAA, 2,4D etc. IBA at the concentration of 4000 ppm is the best plant growth regulator for rooting in cuttings. Gibberellins (GA) are diterpene plant hormones that influence various aspects of growth and development through complex biosynthetic processes. Application of GA with combination of Zinc and pruning showed better performance in fruit weight, ascorbic acid, and reduction in pre-harvest fruit drop. Repeated applications of brassinosteroid have a long-lasting effect on strawberry cv. Winter Dawn physiological growth. Triacontanol (TRIA), natural plant growth hormone in fruit crops. It regulates a variety of physiological processes in plants. Salicylic acid (SA) is a plant hormone best recognized for modulating host responses in response to pathogen infection.SA treatments boosted crop productivity and fruit quality criteria such as firmness, aril color, and individual sugar and organic acid concentrations at harvest. It is revealed by many studies that the application of biofertilizer play an essential role for increasing the sustainability of the soil and also enhance the organic matter content, aeration, fertility, availability of micro and macronutrients with in the soil which are the essential things for the better survival of the plant and results into the good quality and higher yield from the plant. The present review encompasses the use and the effect of different PGR’s and biofertilizer on the fruit crops.

Lipid A heterogeneity and its role in the host interactions with pathogenic and commensal bacteria.

Lipopolysaccharide (LPS) is for most but not all Gram-negative bacteria an essential component of the outer leaflet of the outer membrane. LPS contributes to the integrity of the outer membrane, which acts as an effective permeability barrier to antimicrobial agents and protects against complement-mediated lysis. In commensal and pathogenic bacteria LPS interacts with pattern recognition receptors (e.g LBP, CD14, TLRs) of the innate immune system and thereby plays an important role in determining the immune response of the host. LPS molecules consist of a membrane-anchoring lipid A moiety and the surface-exposed core oligosaccharide and O-antigen polysaccharide. While the basic lipid A structure is conserved among different bacterial species, there is still a huge variation in its details, such as the number, position and chain length of the fatty acids and the decoration of the glucosamine disaccharide with phosphate, phosphoethanolamine or amino sugars. New evidence has emerged over the last few decades on how this lipid A heterogeneity confers distinct benefits to some bacteria because it allows them to modulate host responses in response to changing host environmental factors. Here we give an overview of what is known about the functional consequences of this lipid A structural heterogeneity. In addition, we also summarize new approaches for lipid A extraction, purification and analysis which have enabled analysis of its heterogeneity.