scholarly journals IL-33 regulates age-dependency of long-term immune dysfunction induced by sepsis

2022 ◽  
Author(s):  
David F Colon ◽  
Carlos W Wanderley ◽  
Walter Turato ◽  
Vanessa F Borges ◽  
Marcelo Franchin ◽  
...  

Sepsis survival in adults is commonly followed by immunosuppression and increased susceptibility to secondary infections. However, the long-term immune consequences of pediatric sepsis are unknown. Here, we compared the frequency of Tregs, the activation of the IL-33/ILC2s axis in M2 macrophages, and the DNA methylation of epithelial lung cells from post-septic infant and adult mice. In contrast to adults, infant mice were resistant to secondary infection and did not show impairment in tumour controls upon melanoma challenge. Mechanistically, increased IL-33 levels, Tregs expansion, and activation of ILC2s and M2-macrophages were observed in post-septic adults but not infant mice. Impaired IL-33 production in post-septic infant mice was associated with increased DNA-methylation on lung epithelial cells. Notably, IL-33 treatment boosted the expansion of Tregs and induced immunosuppression in infant mice. Clinically, adults but not pediatric post-septic patients exhibited higher counts of Tregs and sera IL-33 levels. Hence, we describe a crucial and age-dependent role for IL-33 in post-sepsis immunosuppression.

Parasitology ◽  
2001 ◽  
Vol 123 (5) ◽  
pp. 455-463 ◽  
Author(s):  
J. A. JACKSON ◽  
R. C. TINSLEY

The reproductive kinetics of Protopolystoma xenopodis primary and secondary infections in Xenopus laevis were monitored in a 3-year study. Thirty-five naïve, lab-raised, full-sib X. laevis from 1 spawning were each exposed to 30 P. xenopodis eggs. The course of infections at 20 °C was monitored by screening isolated hosts for parasite egg production. Ninety-four percent of toads supported the development of gravid parasites. Infections became patent 9–19 weeks p.i., lasted 3–30 months and produced estimated totals of 1–7152 eggs/host. Variation in primary infection characters was discontinuous: a subgrouping of hosts (16%) was characterized by extended infection duration and low reproductive rate. In order to test the effect of long-term infection history on a subsequent challenge, each host was re-exposed to P. xenopodis infective stages (30 eggs/host) 6 months after the loss of its original infection. Establishment of patent infection was significantly lower (15%), and pre-patent period (12–28 weeks) longer, than in primary infections of the same hosts, and than in concurrently exposed naïve controls (contemporary full-sibs of the primary/secondary infection group, maintained in parallel; n = 28). There was no relationship between primary infection characteristics and secondary infection outcome. Overall reproductive output per initial infective stage for the primary exposure exceeded that for the secondary exposure by a ratio of 15[ratio ]1. Results suggest that primary infection with P. xenopodis can elicit strong, long-term protective immunity against re-infection in X. laevis.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anne-Christine Plank ◽  
Stefan Frey ◽  
Lukas Andreas Basedow ◽  
Jalal Solati ◽  
Fabio Canneva ◽  
...  

AbstractIn our previous study, we found that prenatal trauma exposure leads to an anxiety phenotype in mouse pups, characterized by increased corticosterone levels and increased anxiety-like behavior. In order to understand the mechanisms by which aversive in utero experience leads to these long-lasting behavioral and neuroendocrine changes, we investigated stress reactivity of prenatally traumatized (PT) mice, as well as the expression and methylation levels of several key regulatory genes of the stress axis in the dorsal hippocampus (dHPC) of the PT embryo and adult mice. We detected increased corticotropin-releasing hormone receptor 1 (Crhr1) and decreased FK506 binding protein 5 (Fkbp5) mRNA levels in the left dHPC of adult PT mice. These alterations were accompanied by a decreased methylation status of the Crhr1 promoter and an increased methylation status of the Fkbp5 promoter, respectively. Interestingly, the changes in Fkbp5 and Crhr1 mRNA levels were not detected in the embryonic dHPC of PT mice. Together, our findings provide evidence that prenatal trauma has a long-term impact on stress axis function and anxiety phenotype associated with altered Crhr1 and Fkbp5 transcripts and promoter methylation.


Epigenetics ◽  
2021 ◽  
pp. 1-17
Author(s):  
Gloria C. Chi ◽  
Yongmei Liu ◽  
James W. MacDonald ◽  
Lindsay M. Reynolds ◽  
Daniel A. Enquobahrie ◽  
...  

Lab Animal ◽  
2014 ◽  
Vol 43 (10) ◽  
pp. 353-357 ◽  
Author(s):  
Patrícia O. Ribeiro ◽  
Henrique B. Silva ◽  
Ângelo R. Tomé ◽  
Rodrigo A. Cunha ◽  
Luís M. Antunes

2001 ◽  
Vol 73 (1) ◽  
pp. 41-48 ◽  
Author(s):  
R. R. Woolastont ◽  
R. G. Windon

AbstractData were analysed from a long-term selection experiment with Merino sheep, based on immunological responsiveness to the intestinal nematode Trichostrongylus colubriformis. For the first 14 years of selection, the criterion was the mean of five fortnightly faecal worm-egg counts (FECs) of pen-housed lambs that were vaccinated with irradiated larvae then challenged with normal T. colubriformis larvae. For most of the lambs born in the subsequent 6 years, the selection criterion was the mean of three weekly FECs of grazing lambs following a secondary challenge with T. colubriformis larvae. Data from 2233 lambs were included in the analyses.At the end of the experiment, the lines selected for high and low response to challenge differed by 2·3 to 2·9 phenotypic standard deviations. The heritability of average pen-tested FEC was 0·38 (s.e. 0·04), similar to that for average FEC after secondary field challenge (0·37, s.e. 007). Average FECs from the primary field challenge were less heritable (0·21, s.e. 006). Counts recorded on pen-tested animals at 3, 5, 7, 9 and 11 weeks after infection were all highly correlated genetically (estimates 0·93 to 0·99) and of similar heritability (0·33 to 0·39) with a non-significant tendency for later FECs to be more heritable. Phenotypic correlations were lower, ranging from 0·60 for counts 8 weeks apart, to 0·78 to 0·81 for adjacent samples 2 weeks apart. Single-record heritability estimates at 3, 4 and 5 weeks after secondary infection in grazing lambs did not differ statistically from each other but were highest at the 5th week after infection at 0·33 (s.e. 007).FECs determined in pens were imperfectly correlated with FECs determined at pasture (genetic correlation 0·72, s.e. 013). Phenotypic correlations of single-record FECs across primary and secondary field challenges were low (around 0·2), although the genetic correlation between mean primary FEC and mean secondary FEC was not significantly different from unity. Testing under standardized conditions in pens did not result in consistently higher heritabilities than testing immunologically primed lambs at pasture. Repeated measurement in a breeding programme offers little additional benefit, except when lambs have had ample prior experience of parasite infection, with the two measures separated by an anthelmintic treatment. If an objective of a Merino breeding programme is to reduce FEC under field conditions, then using one measure in the field, approximately 3 to 5 weeks after a secondary artificial infection, is likely to lead to long-term progress.


2016 ◽  
Vol 60 (1) ◽  
Author(s):  
T. Kato ◽  
K. Oka ◽  
T. Nakamura ◽  
A. Ito

<p>Organ-specific stem cells play key roles in maintaining the epithelial cell layers of lung. Bronchioalveolar stem cells (BASCs) are distal lung epithelial stem cells of adult mice. Alveolar type 2 (AT2) cells have important functions and serve as progenitor cells of alveolar type 1 (AT1) cells to repair the epithelium when they are injured. Hepatocyte growth factor (HGF) elicits mitogenic, morphogenic, and anti-apoptotic effects on lung epithelial cells through tyrosine phosphorylation of Met receptor, and thus is recognized as a pulmotrophic factor. To understand which cells HGF targets in lung, we identified the cells expressing Met by immunofluorescence assay. Met was strongly expressed in BASCs, which expressed an AT2 cell marker, pro-SP-C, and a club cell marker, CCSP. In alveoli, we found higher expression of Met in primary AT2 than in AT1 cells, which was confirmed using primary AT2 cells. We further examined the mitogenic activity of HGF in AT2-cell-derived alveolar-like cysts (ALCs) in 3D culture. Multicellular ALCs expressed Met, and HGF enhanced the ALC production. Taking these findings together, BASCs could also be an important target for HGF, and HGF-Met signaling could function more potent on cells that have greater multipotency in adult lung.</p>


2021 ◽  
Vol 6 (1) ◽  
pp. 79
Author(s):  
Etis Duhita Rahayuningtyas ◽  
Indah Suasani Wahyuni ◽  
Irna Sufiawati

ABSTRACTBackground: Stevens-Johnson syndrome (SSJ) is a hypersensitivity reaction that is often triggered by drugs but this case is rare. These reactions result in uncontrolled keratinocyte damage to the skin and mucosa throughout the body, including the oral mucosa, and are often life-threatening. The use of high doses of corticosteroids is a treatment that is often given but it can trigger secondary infections of fungal and viral in the oral cavity. Purpose: This case report discusses the management of oral manifestations and secondary infections in SSJ patients, and becomes guidance for health professionals. Case: A-42-years-old male patient was consulted from the Department of Dermatology and Venereology (DV) due to oral pain and eating difficulties. The severity-of-illness-score for toxic-epidermal-necrolysis (SCORTEN) was 1. Erosive serosanguinous crusts, tend to bleed were found on the lips. Intraoral clinically presented wide erosive lesions and multiple ulcers, accompanied by a pseudomembranous plaque, and teeth decay. Hematologic examination showed an increase in leukocytes, neutrophil segments, monocytes, SGOT, urea, and creatinine as well as decreased hemoglobin, hematocrit, erythrocytes, MCHC, protein, and albumin. Anti-HSV1 IgG increased almost 6 times than normal values. The patient was diagnosed with SJS with oral involvement, secondary infections of pseudomembranous candidiasis, and herpetic stomatitis. Case Management: Systemic therapy given were intravenous dexamethasone, ranitidine, calcium, and cetirizine, from the DV Department, while hydrocortisone lip ointment, Chlorhexidine digluconate 0.12%, and Nystatin oral suspension for oral problems. The lesions progressed in 24 days. Conclusion: Oral secondary infections may occur in SJS patients due to high-dose corticosteroid therapy.Keywords: Herpetic Stomatitis, Oral Manifestation, Oral Secondary Infection, Pseudomembranous Candidiasis, Stevens-Johnson Syndrome.


Sign in / Sign up

Export Citation Format

Share Document