IL-21 Up-Regulates the Expression of Genes Associated with Innate Immunity and Th1 Response

Sericea Lespedeza (SL), is a high-quality, low input forage that suppresses gastro-intestinal parasites in goats. The effect of dietary SL on the expression of genes involved in innate immunity in goats has not been established. The objective of this study was to evaluate the impact of a diet containing SL on the expression of genes involved in innate immunity in goat blood. Blood was collected by jugular venipuncture from goats fed a diet of 75% SL (n = 9) and a control group (n = 7), fed a SL free diet. Blood was used to evaluate expression of (CD-14, TLR-2, TLR-4, IL-10, IL-8, IL-2, INF-r, and TNF-a). Serum was extracted and used for evaluation of the secretion of pro-inflammatory cytokines (TNF-a, IFNr, granulocyte colony stimulating factor (GCSF), granulocyte-macrophage colony-stimulating factor (GMCSF), IL-1a, IL-8, IP-10 and RANTES) using a commercial ELISA kit. The level of gene expression of CD-14, TLR-2, TLR-4, IL-10, IL-8, IL-2, INF-r, and TNF-a was higher in treated animals compared to control. The Sericea Lespedeza diet affected the secretion of pro-inflammatory cytokines by increasing the serum levels of TNF-a, IFNr, GCSF, GMCSF, IL-1a, IP-10 (P < 0.0002), and by decreasing (P < 0.0001) IL-8 and RANTES in blood from goats fed SL. This suggests that dietary tannins modulate gene expression and may affect the goat's innate immune response in blood. Further research is needed to understand and harness the effect of dietary condensed tannins to modulate innate immunity in goats.

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Coronavirus infection and PARP expression dysregulate the NAD metabolome: An actionable component of innate immunity

Journal of Biological Chemistry ◽

10.1074/jbc.ra120.015138 ◽

2020 ◽

Vol 295 (52) ◽

pp. 17986-17996 ◽

Cited By ~ 1

Author(s):

Collin D. Heer ◽

Daniel J. Sanderson ◽

Lynden S. Voth ◽

Yousef M. O. Alhammad ◽

Mark S. Schmidt ◽

...

Keyword(s):

Innate Immunity ◽

Hepatitis Virus ◽

Murine Hepatitis Virus ◽

Nicotinamide Riboside ◽

Antiviral Responses ◽

Expression Of Genes ◽

Nad Synthesis ◽

Genes Encoding ◽

Antiviral Activities ◽

A Chain

Poly(ADP-ribose) polymerase (PARP) superfamily members covalently link either a single ADP-ribose (ADPR) or a chain of ADPR units to proteins using NAD as the source of ADPR. Although the well-known poly(ADP-ribosylating) (PARylating) PARPs primarily function in the DNA damage response, many noncanonical mono(ADP-ribosylating) (MARylating) PARPs are associated with cellular antiviral responses. We recently demonstrated robust up-regulation of several PARPs following infection with murine hepatitis virus (MHV), a model coronavirus. Here we show that SARS-CoV-2 infection strikingly up-regulates MARylating PARPs and induces the expression of genes encoding enzymes for salvage NAD synthesis from nicotinamide (NAM) and nicotinamide riboside (NR), while down-regulating other NAD biosynthetic pathways. We show that overexpression of PARP10 is sufficient to depress cellular NAD and that the activities of the transcriptionally induced enzymes PARP7, PARP10, PARP12 and PARP14 are limited by cellular NAD and can be enhanced by pharmacological activation of NAD synthesis. We further demonstrate that infection with MHV induces a severe attack on host cell NAD+ and NADP+. Finally, we show that NAMPT activation, NAM, and NR dramatically decrease the replication of an MHV that is sensitive to PARP activity. These data suggest that the antiviral activities of noncanonical PARP isozyme activities are limited by the availability of NAD and that nutritional and pharmacological interventions to enhance NAD levels may boost innate immunity to coronaviruses.

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Some aspects of development of typhoid fever and persistent brucellosis infection

Epidemiology and Infectious Diseases (Russian Journal) ◽

10.17816/eid35180 ◽

2020 ◽

Vol 25 (1) ◽

pp. 35-40

Author(s):

Marina N. Bojchenko ◽

Elena O. Kravtsova ◽

Elena V. Budanova ◽

Olga F. Belaia ◽

Natalya V. Maloletneva ◽

...

Keyword(s):

Immune Response ◽

Innate Immunity ◽

Typhoid Fever ◽

Chronic Infection ◽

Effector Proteins ◽

Sources Of Information ◽

Salmonella Spp ◽

Expression Of Genes ◽

Causative Agents ◽

Vi Antigen

Bacterial vacuolated intracellular parasites, such as Salmonella spp. and Brucella spp., possess the ability to cause persistent, long-life chronic infection during which the microbe continues to replicate inside the host organism in spite of the development of an immune response. Such bacteria develop a strategy to evade the immune response, which plays a key role in the development of chronic infection. The implementation of this strategy is aimed at inhibiting the action of factors of innate immunity. In brucella, this process is mediated by the noncanonical structure of lipopolysaccharide (LPS), as a result of which the pathogen is not recognized by the cells of innate immunity, as well as by the functioning of T4CC, the effector proteins of which block the development of the inflammatory response. The strategy of S. Typhi is realized via the expression of genes of pathogenicity island 7 encoding Vi-antigen and genotoxin. Vi-antigen inhibits recognition of the microbe by cells of the innate immune system. Typhoid genotoxin causes the death of immune cells. Brucella realizes this strategy via the noncanonical structure of LPS and T4SS, effector proteins of which block the development of inflammation. Alternative activated macrophages appear during chronic infection caused by both pathogens. These microbes are able to regulate the metabolism of macrophages according to their needs while persisting in them. A review of the sources of information on this problem allows us to conclude that both the causative agent of typhoid fever S. Typhi and the causative agents of brucellosis use the same strategies for the development of a chronic infectious process, but the implementation of these strategies is carried out specifically.

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Induction and suppression of rice innate immunity

Indian Journal of Genetics and Plant Breeding (The) ◽

10.31742/ijgpb.79s.1.6 ◽

2019 ◽

Vol 79 (01S) ◽

Author(s):

Kamal Kumar Malukani ◽

Shakuntala E. Pillai ◽

Neha R. Kachewar ◽

Hitendra K. Patel ◽

Ramesh V. Sonti

Keyword(s):

Innate Immunity ◽

Immune Responses ◽

Calcium Ions ◽

Defense Responses ◽

Oxygen Species ◽

Signal Transduction Cascade ◽

Expression Of Genes ◽

Associated Functions ◽

Enhanced Expression ◽

Host Tissues

The rice plant is infected by a number of pathogens which cause significant losses of yield. Plants possess inducible innate immunity by which they can perceive danger and mount defense responses. Recognition of the pathogen is a crucial step in induction of plant immune responses. Plants can recognise a wide category of molecules related either to conserved components of pathogen structures, pathogen secreted molecules or plant damage-associated molecules. Recognition of these molecules/elicitors by receptors initiates a signal transduction cascade which includes phosphorylation of various intermediate proteins, influx of calcium ions, production of reactive oxygen species and synthesis of phytohormones. The signaling intermediates also activate transcription factors leading to enhanced expression of genes related to defense associated functions. As immune responses are energy intensive processes, they are tightly regulated through phosphorylation/dephosphorylation events or through degradation of signalling intermediates. The activation of plant innate immunity suppresses multiplication and spread of pathogen within the host tissues. In this review we discuss about key molecular players involved in rice immune responses.

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Coronavirus infection and PARP expression dysregulate the NAD Metabolome: an actionable component of innate immunity

10.1101/2020.04.17.047480 ◽

2020 ◽

Cited By ~ 11

Author(s):

Collin D. Heer ◽

Daniel J. Sanderson ◽

Lynden S. Voth ◽

Yousef M.O. Alhammad ◽

Mark S. Schmidt ◽

...

Keyword(s):

Innate Immunity ◽

Hepatitis Virus ◽

Murine Hepatitis Virus ◽

Nicotinamide Riboside ◽

Antiviral Responses ◽

Expression Of Genes ◽

Nad Synthesis ◽

Genes Encoding ◽

Antiviral Activities ◽

A Chain

ABSTRACTPoly-ADP-ribose polymerase (PARP) superfamily members covalently link either a single ADP-ribose (ADPR) or a chain of ADPR units to proteins using nicotinamide adenine dinucleotide (NAD) as the source of ADPR. While the well-known poly-ADP-ribosylating (PARylating) PARPs primarily function in the DNA damage response, many non-canonical mono-ADP-ribosylating (MARylating) PARPs are associated with cellular antiviral responses. We recently demonstrated robust upregulation of several PARPs following infection with Murine Hepatitis Virus (MHV), a model coronavirus. Here we show that SARS-CoV-2 infection strikingly upregulates MARylating PARPs and induces the expression of genes encoding enzymes for salvage NAD synthesis from nicotinamide (NAM) and nicotinamide riboside (NR), while downregulating other NAD biosynthetic pathways. We show that overexpression of PARP10 is sufficient to depress cellular NAD and that the activities of the transcriptionally induced enzymes PARP7, PARP10, PARP12 and PARP14 are limited by cellular NAD and can be enhanced by pharmacological activation of NAD synthesis. We further demonstrate that infection with MHV induces a severe attack on host cell NAD+ and NADP+. Finally, we show that NAMPT activation, NAM and NR dramatically decrease the replication of an MHV virus that is sensitive to PARP activity. These data suggest that the antiviral activities of noncanonical PARP isozyme activities are limited by the availability of NAD, and that nutritional and pharmacological interventions to enhance NAD levels may boost innate immunity to coronaviruses.

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Changes in bacterial community and expression of genes involved in intestinal innate immunity in the jejunum of newborn lambs during the first 24 hours of life

Journal of Dairy Science ◽

10.3168/jds.2020-19888 ◽

2021 ◽

Author(s):

H.L. Zhu ◽

X.W. Zhao ◽

R.W. Han ◽

Q.J. DU ◽

Y.X. Qi ◽

...

Keyword(s):

Innate Immunity ◽

Bacterial Community ◽

Expression Of Genes

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Strategies for Using Muramyl Peptides - Modulators of Innate Immunity of Bacterial Origin - in Medicine

Frontiers in Immunology ◽

10.3389/fimmu.2021.607178 ◽

2021 ◽

Vol 12 ◽

Author(s):

Svetlana V. Guryanova ◽

Rahim M. Khaitov

Keyword(s):

Innate Immunity ◽

Immunological Tolerance ◽

The Body ◽

New Drugs ◽

Antimicrobial Drugs ◽

Chemotherapy Drugs ◽

Mhc Molecules ◽

Expression Of Genes ◽

Oncological Diseases ◽

Cancer Mutations

The spread of infectious diseases is rampant. The emergence of new infections, the irrational use of antibiotics in medicine and their widespread use in agriculture contribute to the emergence of microorganisms that are resistant to antimicrobial drugs. By 2050, mortality from antibiotic-resistant strains of bacteria is projected to increase up to 10 million people per year, which will exceed mortality from cancer. Mutations in bacteria and viruses are occurring faster than new drugs and vaccines are being introduced to the market. In search of effective protection against infections, new strategies and approaches are being developed, one of which is the use of innate immunity activators in combination with etiotropic chemotherapy drugs. Muramyl peptides, which are part of peptidoglycan of cell walls of all known bacteria, regularly formed in the body during the breakdown of microflora and considered to be natural regulators of immunity. Their interaction with intracellular receptors launches a sequence of processes that ultimately leads to the increased expression of genes of MHC molecules, pro-inflammatory mediators, cytokines and their soluble and membrane-associated receptors. As a result, all subpopulations of immunocompetent cells are activated: macrophages and dendritic cells, neutrophils, T-, B- lymphocytes and natural killer cells for an adequate response to foreign or transformed antigens, manifested both in the regulation of the inflammatory response and in providing immunological tolerance. Muramyl peptides take part in the process of hematopoiesis, stimulating production of colony-stimulating factors, which is the basis for their use in the treatment of oncological diseases. In this review we highlight clinical trials of drugs based on muramyl peptides, as well as clinical efficacy of drugs mifamurtide, lycopid, liasten and polimuramil. Such a multifactorial effect of muramyl peptides and a well-known mechanism of activity make them promising drugs in the treatment and preventing of infectious, allergic and oncological diseases, and in the composition of vaccines.

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