scholarly journals Immune Profile of the Nasal Mucosa in Patients with Cutaneous Leishmaniasis

2020 ◽  
Vol 88 (5) ◽  
Author(s):  
María J. Gómez-Zafra ◽  
Adriana Navas ◽  
Jimena Jojoa ◽  
Julieth Murillo ◽  
Camila González ◽  
...  

ABSTRACT Localized skin lesions are characteristic of cutaneous leishmaniasis (CL); however, Leishmania (Viannia) species, which are responsible for most CL cases in the Americas, can spread systemically, sometimes resulting in mucosal disease. Detection of Leishmania has been documented in healthy mucosal tissues (conjunctiva, tonsils, and nasal mucosa) and healthy skin of CL patients and in individuals with asymptomatic infection in areas of endemicity of L. (V.) panamensis and L. (V.) braziliensis transmission. However, the conditions and mechanisms that favor parasite persistence in healthy mucosal tissues are unknown. In this descriptive study, we compared the cell populations of the nasal mucosa (NM) of healthy donors and patients with active CL and explored the immune gene expression signatures related to molecular detection of Leishmania in this tissue in the absence of clinical signs or symptoms of mucosal disease. The cellular composition and gene expression profiles of NM samples from active CL patients were similar to those of healthy volunteers, with a predominance of epithelial over immune cells, and within the CD45+ cell population, a higher frequency of CD66b+ followed by CD14+ and CD3+ cells. In CL patients with molecular evidence of Leishmania persistence in the NM, genes characteristic of an anti-inflammatory and tissue repair responses (IL4R, IL5RA, POSTN, and SATB1) were overexpressed relative to NM samples from CL patients in which Leishmania was not detected. Here, we report the first immunological description of subclinically infected NM tissues of CL patients and provide evidence of a local anti-inflammatory environment favoring parasite persistence in the NM.

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Ruoxi Yu ◽  
Yin Yang ◽  
Yuanyuan Han ◽  
Pengwei Hou ◽  
Yingshuai Li ◽  
...  

Objectives. Differences among healthy subjects and associated disease risks are of substantial interest in clinical medicine. According to the theory of “constitution-disease correlation” in traditional Chinese medicine, we try to find out if there is any connection between intolerance of cold in Yang deficiency constitution and molecular evidence and if there is any gene expression basis in specific disorders. Methods. Peripheral blood mononuclear cells were collected from Chinese Han individuals with Yang deficiency constitution (n=20) and balanced constitution (n=8) (aged 18–28) and global gene expression profiles were determined between them using the Affymetrix HG-U133 Plus 2.0 array. Results. The results showed that when the fold change was ≥1.2 and q ≤ 0.05, 909 genes were upregulated in the Yang deficiency constitution, while 1189 genes were downregulated. According to our research differential genes found in Yang deficiency constitution were usually related to lower immunity, metabolic disorders, and cancer tendency. Conclusion. Gene expression disturbance exists in Yang deficiency constitution, which corresponds to the concept of constitution and gene classification. It also suggests people with Yang deficiency constitution are susceptible to autoimmune diseases, enteritis, arthritis, metabolism disorders, and cancer, which provides molecular evidence for the theory of “constitution-disease correlation.”


2021 ◽  
Vol 22 (4) ◽  
pp. 1901
Author(s):  
Brielle Jones ◽  
Chaoyang Li ◽  
Min Sung Park ◽  
Anne Lerch ◽  
Vimal Jacob ◽  
...  

Mesenchymal stromal cells derived from the fetal placenta, composed of an amnion membrane, chorion membrane, and umbilical cord, have emerged as promising sources for regenerative medicine. Here, we used next-generation sequencing technology to comprehensively compare amniotic stromal cells (ASCs) with chorionic stromal cells (CSCs) at the molecular and signaling levels. Principal component analysis showed a clear dichotomy of gene expression profiles between ASCs and CSCs. Unsupervised hierarchical clustering confirmed that the biological repeats of ASCs and CSCs were able to respectively group together. Supervised analysis identified differentially expressed genes, such as LMO3, HOXA11, and HOXA13, and differentially expressed isoforms, such as CXCL6 and HGF. Gene Ontology (GO) analysis showed that the GO terms of the extracellular matrix, angiogenesis, and cell adhesion were significantly enriched in CSCs. We further explored the factors associated with inflammation and angiogenesis using a multiplex assay. In comparison with ASCs, CSCs secreted higher levels of angiogenic factors, including angiogenin, VEGFA, HGF, and bFGF. The results of a tube formation assay proved that CSCs exhibited a strong angiogenic function. However, ASCs secreted two-fold more of an anti-inflammatory factor, TSG-6, than CSCs. In conclusion, our study demonstrated the differential gene expression patterns between ASCs and CSCs. CSCs have superior angiogenic potential, whereas ASCs exhibit increased anti-inflammatory properties.


2019 ◽  
Vol 88 (3) ◽  
Author(s):  
Adriana Navas ◽  
Olga Fernández ◽  
Carolina Gallego-Marín ◽  
María del Mar Castro ◽  
Mariana Rosales-Chilama ◽  
...  

ABSTRACT The immune mechanisms that contribute to the efficacy of treatment of cutaneous leishmaniasis (CL) are not fully understood. The aim of this study was to define immune correlates of the outcome of treatment of CL caused by Leishmania (Viannia) species during standard of care treatment with pentavalent antimonials. We conducted a comparative expression profiling of immune response genes in peripheral blood mononuclear cells (PBMCs) and lesion biopsy specimens obtained from CL patients before and at the end of treatment (EoT) with meglumine antimoniate. The ex vivo response of PBMCs to L. (V.) panamensis partially reflected that of lesion microenvironments. Significant downregulation of gene expression profiles consistent with local innate immune responses (monocyte and neutrophil activation and chemoattractant molecules) was observed at EoT in biopsy specimens of patients who cured (n = 8), compared to those from patients with treatment failure (n = 8). Among differentially expressed genes, pretreatment expression of CCL2 was significantly predictive of the therapeutic response (receiver operating characteristic [ROC] curve, area under the curve [AUC] = 0.82, P = 0.02). Polymorphisms in regulatory regions of the CCL2 promoter were analyzed in a pilot cohort of DNA samples from CL patients (cures, n = 20, and treatment failure, n = 20), showing putative association of polymorphisms rs13900(C/T) and rs2857656(G/C) with treatment outcome. Our data indicate that dampening gene expression profiles of monocyte and neutrophil activation characterize clinical cure after treatment of CL, supporting participation of parasite-sustained inflammation or deregulated innate immune responses in treatment failure.


Blood ◽  
2004 ◽  
Vol 104 (3) ◽  
pp. 675-686 ◽  
Author(s):  
Wolfgang Wagner ◽  
Alexandra Ansorge ◽  
Ute Wirkner ◽  
Volker Eckstein ◽  
Christian Schwager ◽  
...  

AbstractThe molecular mechanisms that regulate asymmetric divisions of hematopoietic progenitor cells (HPCs) are not yet understood. The slow-dividing fraction (SDF) of HPCs is associated with primitive function and self-renewal, whereas the fast-dividing fraction (FDF) predominantly proceeds to differentiation. CD34+/CD38– cells of human umbilical cord blood were separated into the SDF and FDF. Genomewide gene expression analysis of these populations was determined using the newly developed Human Transcriptome Microarray containing 51 145 cDNA clones of the Unigene Set-RZPD3. In addition, gene expression profiles of CD34+/CD38– cells were compared with those of CD34+/CD38+ cells. Among the genes showing the highest expression levels in the SDF were the following: CD133, ERG, cyclin G2, MDR1, osteopontin, CLQR1, IFI16, JAK3, FZD6, and HOXA9, a pattern compatible with their primitive function and self-renewal capacity. Furthermore, morphologic differences between the SDF and FDF were determined. Cells in the SDF have more membrane protrusions and CD133 is located on these lamellipodia. The majority of cells in the SDF are rhodamine-123dull. These results provide molecular evidence that the SDF is associated with primitive function and serves as basis for a detailed understanding of asymmetric division of stem cells.


2013 ◽  
Vol 162 (2-4) ◽  
pp. 519-529 ◽  
Author(s):  
Chun-Ming Lin ◽  
Chian-Ren Jeng ◽  
Jen-Pei Liu ◽  
En-Chung Lin ◽  
Chih-Cheng Chang ◽  
...  

2004 ◽  
Vol 17 (2) ◽  
pp. 201-214 ◽  
Author(s):  
Jonathan Z. Pan ◽  
Rebecka Jörnsten ◽  
Ronald P. Hart

Inflammatory responses contribute to secondary tissue damage following spinal cord injury (SCI). A potent anti-inflammatory glucocorticoid, methylprednisolone (MP), is the only currently accepted therapy for acute SCI but its efficacy has been questioned. To search for additional anti-inflammatory compounds, we combined microarray analysis with an explanted spinal cord slice culture injury model. We compared gene expression profiles after treatment with MP, acetaminophen, indomethacin, NS398, and combined cytokine inhibitors (IL-1ra and soluble TNFR). Multiple gene filtering methods and statistical clustering analyses were applied to the multi-dimensional data set and results were compared. Our analysis showed a consistent and unique gene expression profile associated with NS398, the selective cyclooxygenase-2 (COX-2) inhibitor, in which the overall effect of these upregulated genes could be interpreted as neuroprotective. In vivo testing demonstrated that NS398 reduced lesion volumes, unlike MP or acetaminophen, consistent with a predicted physiological effect in spinal cord. Combining explanted spinal cultures, microarrays, and flexible clustering algorithms allows us to accelerate selection of compounds for in vivo testing.


2012 ◽  
Vol 108 (7) ◽  
pp. 1226-1234 ◽  
Author(s):  
T. Sweeney ◽  
C. B. Collins ◽  
P. Reilly ◽  
K. M. Pierce ◽  
M. Ryan ◽  
...  

β-Glucans have been identified as natural biomolecules with immunomodulatory activity. The first objective of the present study was to compare the effects of purified β-glucans derived from Laminariadigitata, L. hyperborea and Saccharomyces cerevisiae on piglet performance, selected bacterial populations and intestinal volatile fatty acid (VFA) production. The second aim was to compare the gene expression profiles of the markers of pro- and anti-inflammation in both unchallenged and lipopolysaccharide (LPS)-challenged ileal and colonic tissues. β-Glucans were included at 250 mg/kg in the diets. The β-glucans derived from L. hyperborea, L. digitata and S. cerevisiae all reduced the Enterobacteriaceae population (P < 0·05) without influencing the lactobacilli and bifidobacteria populations (P>0·05) in the ileum and colon. There was a significant interaction between gastrointestinal region and β-glucan source in the expression of cytokine markers, IL-1α (P < 0·001), IL-10 (P < 0·05), TNF-α (P < 0·05) and IL-17A (P < 0·001). β-Glucans did not stimulate any pro- or anti-inflammatory cytokine markers in the ileal epithelial cells. In contrast, the expression of a panel of pro- and anti-inflammatory cytokines (IL-1α, IL-10, TNF-α and IL-17A) was down-regulated in the colon following exposure to β-glucans from all the three sources. However, the data suggest that the soluble β-glucans derived from L. digitata may be acting via a different mechanism from the insoluble β-glucans derived from L. hyperborea and S. cerevisiae, as the VFA profile was different in the L. digitata-treated animals. There was an increase in IL-8 gene expression (P < 0·05) in the gastrointestinal tract from the animals exposed to L. digitata following an LPS ex vivo challenge that was not evident in the other two treatment groups. In conclusion, β-glucans from both seaweed and yeast sources reduce Enterobacteriaceae counts and pro-inflammatory markers in the colon, though the mechanisms of action may be different between the soluble and insoluble fibre sources.


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