Increased vitamin D receptor expression from macrophages after stimulation with M. tuberculosis among persons who have recovered from extrapulmonary tuberculosis

Fiske, Christina T.; Blackman, Amondrea; Maruri, Fernanda; Rebeiro, Peter F; Huamán, Moisés A.; Kator, Jamie L.; Algood, Holly M. Scott

doi:10.1186/s12879-019-3958-7

Cited by 16 publications

(15 citation statements)

References 44 publications

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“…In spite of all common genes were concordant between treatments, SLCO4A1 and VRD had different RNA levels in response to LPS (upregulated) and Poly (I:C) (downregulated) treatment at 6h ( Supplementary Figure S5 ). Both SLCO4A1 and VRD have been reported to be part of the RNA response to bacterial ( Dower et al, 2008 ; Fiske et al, 2019 ) or viral infections ( Petrovic and Piquette-Miller, 2010 ; Gotlieb et al, 2018 ). In addition, we observed differential expression in three members of the interferon (IFN) gene family IFNA1 , IFNB1 and porcine IFN-ALPHAOMEGA ( Li et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Changes in H3K27ac at Gene Regulatory Regions in Porcine Alveolar Macrophages Following LPS or PolyIC Exposure

Herrera-Uribe

Byrne

et al. 2020

Front. Genet.

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Changes in chromatin structure, especially in histone modifications (HMs), linked with chromatin accessibility for transcription machinery, are considered to play significant roles in transcriptional regulation. Alveolar macrophages (AM) are important immune cells for protection against pulmonary pathogens, and must readily respond to bacteria and viruses that enter the airways. Mechanism(s) controlling AM innate response to different pathogen-associated molecular patterns (PAMPs) are not well defined in pigs. By combining RNA sequencing (RNA-seq) with chromatin immunoprecipitation and sequencing (ChIP-seq) for four histone marks (H3K4me3, H3K4me1, H3K27ac and H3K27me3), we established a chromatin state map for AM stimulated with two different PAMPs, lipopolysaccharide (LPS) and Poly(I:C), and investigated the potential effect of identified histone modifications on transcription factor binding motif (TFBM) prediction and RNA abundance changes in these AM. The integrative analysis suggests that the differential gene expression between non-stimulated and stimulated AM is significantly associated with changes in the H3K27ac level at active regulatory regions. Although global changes in chromatin states were minor after stimulation, we detected chromatin state changes for differentially expressed genes involved in the TLR4, TLR3 and RIG-I signaling pathways. We found that regions marked by H3K27ac genomewide were enriched for TFBMs of TF that are involved in the inflammatory response. We further documented that TF whose expression was induced by these stimuli had TFBMs enriched within H3K27ac-marked regions whose chromatin state changed by these same stimuli. Given that the dramatic transcriptomic changes and minor chromatin state changes occurred in response to both stimuli, we conclude that regulatory elements (i.e. active promoters) that contain transcription factor binding motifs were already active/poised in AM for immediate inflammatory response to PAMPs. In summary, our data provides the first chromatin state map of porcine AM in response to bacterial and viral PAMPs, contributing to the Functional Annotation of Animal Genomes (FAANG) project, and demonstrates the role of HMs, especially H3K27ac, in regulating transcription in AM in response to LPS and Poly(I:C).

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Section: Discussionmentioning

confidence: 99%

Changes in H3K27ac at Gene Regulatory Regions in Porcine Alveolar Macrophages Following LPS or PolyIC Exposure

Herrera-Uribe

Byrne

et al. 2020

Front. Genet.

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“…In the U.S. study population, a convenience sample of available specimens from a previous study was used (33). In the Brazil study population, sample size was determined based on power of 80% (alpha error, 5%) to detect differences in median frequencies of T-cell subsets >2.5% between EPTB cases and TST negative controls, based on a previous study from our group (30).…”

Section: Discussionmentioning

confidence: 99%

Increased Frequency of Memory CD4+ T-Cell Responses in Individuals With Previously Treated Extrapulmonary Tuberculosis

et al. 2020

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Extrapulmonary TB (EPTB) occurs with increased frequency in persons with underlying immunodeficiency. Even after recovery from acute illness, differences in immune phenotype and activation persist. Studies defining characteristics of immune responses after recovery from extrapulmonary TB may provide insights into factors that increase TB risk. We performed two case-control studies (in the United States and Brazil) among HIV-seronegative adults with previous EPTB (n = 9; 25), previous pulmonary TB (n = 7; 25), latent M. tuberculosis (Mtb) infection (n = 11; 25), and uninfected TB contacts (n = 10; 25). We assessed the frequency of dual CD4+ interferon-γ and tumor necrosis factor-α responses after stimulation with overlapping Mtb peptides from ESAT-6 or CFP-10, or gamma-irradiated Mtb H37Rv, proliferative responses to Mtb antigens, T-regulatory cell (Treg) frequency and phenotype. In both study populations, individuals with prior EPTB had the highest frequency of intracellular cytokine-producing cells in response to Mtb antigens (p < 0.05; p <.0001). Persons with prior EPTB in Brazil had the highest levels of CD4 proliferation to Mtb antigens (p < 0.0001), and the highest expression of CD39 on Tregs (p < 0.0001). Individuals with treated EPTB maintained high frequencies of Mtb-specific memory responses and active Treg cells, suggesting that susceptibility to EPTB occurs despite the ability to develop and maintain enhanced adaptive immune responses.

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“…Importantly, IFNγ and downstream vitamin D-dependent antimicrobial genes are preferentially expressed in TT and T1R skin lesions (79)(80)(81). Furthermore, the vitamin D-antimicrobial pathway is mediated via the vitamin D receptor (VDR), expressed by macrophages in response to TLR1 and TLR2 stimulation (82). Genotyping analysis identified an association of two functional VDR polymorphisms with leprosy phenotypes, including a missense M1T polymorphism (rs2228570; also known as FokI) of a VDR isoform associated with T1R (83).…”

Section: Tgf-βmentioning

confidence: 99%

Host-Related Laboratory Parameters for Leprosy Reactions

et al. 2021

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Leprosy reactions are acute inflammatory episodes that complicate the course of a Mycobacterium leprae infection and are the major cause of leprosy-associated pathology. Two types of leprosy reactions with relatively distinct pathogenesis and clinical features can occur: type 1 reaction, also known as reversal reaction, and type 2 reaction, also known as erythema nodosum leprosum. These acute nerve-destructive immune exacerbations often cause irreversible disabilities and deformities, especially when diagnosis is delayed. However, there is no diagnostic test to detect or predict leprosy reactions before the onset of clinical symptoms. Identification of biomarkers for leprosy reactions, which impede the development of symptoms or correlate with early-onset, will allow precise diagnosis and timely interventions to greatly improve the patients' quality of life. Here, we review the progress of research aimed at identifying biomarkers for leprosy reactions, including its correlation with not only immunity but also genetics, transcripts, and metabolites, providing an understanding of the immune dysfunction and inflammation that underly the pathogenesis of leprosy reactions. Nevertheless, no biomarkers that can reliably predict the subsequent occurrence of leprosy reactions from non-reactional patients and distinguish type I reaction from type II have yet been found.

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Increased vitamin D receptor expression from macrophages after stimulation with M. tuberculosis among persons who have recovered from extrapulmonary tuberculosis

Cited by 16 publications

References 44 publications

Changes in H3K27ac at Gene Regulatory Regions in Porcine Alveolar Macrophages Following LPS or PolyIC Exposure

Changes in H3K27ac at Gene Regulatory Regions in Porcine Alveolar Macrophages Following LPS or PolyIC Exposure

Increased Frequency of Memory CD4+ T-Cell Responses in Individuals With Previously Treated Extrapulmonary Tuberculosis

Host-Related Laboratory Parameters for Leprosy Reactions

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