FRI0164 Innate Immune Stimulation Triggers Altered IL-1A/B Gene Expression and Experimental Spondyloarthritis in Hla-B27/Huβ2M Transgenic Rats

Abstract Background Age-related changes in adaptive and innate immune cells have been associated with a decline in effective immunity and chronic, low-grade inflammation. Epigenetic, transcriptional, and functional changes in monocytes occur with aging, though most studies to date have focused on differences between young adults and the elderly in populations with European ancestry; few data exist regarding changes that occur in circulating monocytes during the first few decades of life or in African populations. We analyzed DNA methylation profiles, cytokine production, and inflammatory gene expression profiles in monocytes from young adults and children from western Kenya. Results We identified several hypo- and hyper-methylated CpG sites in monocytes from Kenyan young adults vs. children that replicated findings in the current literature of differential DNA methylation in monocytes from elderly persons vs. young adults across diverse populations. Differentially methylated CpG sites were also noted in gene regions important to inflammation and innate immune responses. Monocytes from Kenyan young adults vs. children displayed increased production of IL-8, IL-10, and IL-12p70 in response to TLR4 and TLR2/1 stimulation as well as distinct inflammatory gene expression profiles. Conclusions These findings complement previous reports of age-related methylation changes in isolated monocytes and provide novel insights into the role of age-associated changes in innate immune functions.

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Lactobacillus GG prevents recurrence of colitis in HLA-B27 transgenic rats after antibiotic treatment

Gastroenterology ◽

10.1016/s0016-5085(00)85400-1 ◽

2000 ◽

Vol 118 (4) ◽

pp. A814 ◽

Cited By ~ 4

Author(s):

Levinus A. Dieleman ◽

Marije S. Goerres ◽

Annemarie Arends ◽

Dave Sprengers ◽

Robin L. Vamey ◽

...

Keyword(s):

Antibiotic Treatment ◽

Hla B27 ◽

Transgenic Rats ◽

Lactobacillus Gg

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Critical Role of Plasmacytoid Dendritic Cells in Regulating Gene Expression and Innate Immune Responses to Human Rhinovirus-16

Frontiers in Immunology ◽

10.3389/fimmu.2017.01351 ◽

2017 ◽

Vol 8 ◽

Cited By ~ 6

Author(s):

Yang Xi ◽

Niamh M. Troy ◽

Denise Anderson ◽

Olga M. Pena ◽

Jason P. Lynch ◽

...

Keyword(s):

Gene Expression ◽

Dendritic Cells ◽

Immune Responses ◽

Critical Role ◽

Plasmacytoid Dendritic Cells ◽

Innate Immune ◽

Human Rhinovirus ◽

Innate Immune Responses

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HLA-B27 and Human β2-Microglobulin Affect the Gut Microbiota of Transgenic Rats

PLoS ONE ◽

10.1371/journal.pone.0105684 ◽

2014 ◽

Vol 9 (8) ◽

pp. e105684 ◽

Cited By ~ 133

Author(s):

Phoebe Lin ◽

Mary Bach ◽

Mark Asquith ◽

Aaron Y. Lee ◽

Lakshmi Akileswaran ◽

...

Keyword(s):

Gut Microbiota ◽

Hla B27 ◽

Transgenic Rats ◽

Β2 Microglobulin

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Beta 2-microglobulin amyloid deposit in HLA-B27 transgenic rats

Modern Rheumatology ◽

10.3109/s10165-007-0624-5 ◽

2007 ◽

Vol 17 (5) ◽

pp. 380-384 ◽

Cited By ~ 9

Author(s):

Shigeo Fukunishi ◽

Kohsei Yoh ◽

Seiya Kamae ◽

Shinichi Yoshiya

Keyword(s):

Amyloid Deposit ◽

Hla B27 ◽

Transgenic Rats ◽

Beta 2 ◽

Beta 2 Microglobulin

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No Change, No Life? What We Know about Phase Variation in Staphylococcus aureus

Microorganisms ◽

10.3390/microorganisms9020244 ◽

2021 ◽

Vol 9 (2) ◽

pp. 244

Author(s):

Vishal Gor ◽

Ryosuke L. Ohniwa ◽

Kazuya Morikawa

Keyword(s):

Gene Expression ◽

Staphylococcus Aureus ◽

High Frequency ◽

Direct Evidence ◽

Bacterial Species ◽

Phase Variation ◽

Opportunistic Pathogen ◽

Adaptation Strategy ◽

Innate Immune ◽

Epigenetic Mechanisms

Phase variation (PV) is a well-known phenomenon of high-frequency reversible gene-expression switching. PV arises from genetic and epigenetic mechanisms and confers a range of benefits to bacteria, constituting both an innate immune strategy to infection from bacteriophages as well as an adaptation strategy within an infected host. PV has been well-characterized in numerous bacterial species; however, there is limited direct evidence of PV in the human opportunistic pathogen Staphylococcus aureus. This review provides an overview of the mechanisms that generate PV and focuses on earlier and recent findings of PV in S. aureus, with a brief look at the future of the field.

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Characterization of Host Responses duringPseudomonas aeruginosaAcute Infection in the Lungs and Blood and after Treatment with the Synthetic Immunomodulatory Peptide IDR-1002

Infection and Immunity ◽

10.1128/iai.00661-18 ◽

2018 ◽

Vol 87 (1) ◽

Cited By ~ 8

Author(s):

Kelli Wuerth ◽

Amy H. Y. Lee ◽

Reza Falsafi ◽

Erin E. Gill ◽

Robert E. W. Hancock

Keyword(s):

Gene Expression ◽

Bacterial Resistance ◽

Lymphocyte Activation ◽

Lavage Fluid ◽

Innate Immune ◽

Microbial Infection ◽

Content Type ◽

Innate Defense ◽

Lung Infections

ABSTRACTPseudomonas aeruginosais an opportunistic pathogen that causes nosocomial pneumonia and infects patients with cystic fibrosis.P. aeruginosalung 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 acuteP. aeruginosalung infectionin 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 ofP. aeruginosa, IDR-1002, and the combination ofP. aeruginosaand IDR-1002 were evaluated. Differential gene expression analysis showed thatP. aeruginosaincreased 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 treatingP. aeruginosaacute lung infections and associated inflammation.

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