scholarly journals Comparative modulation of lncRNAs in wild-type and rag1-heterozygous mutant zebrafish exposed to immune challenge with spring viraemia of carp virus (SVCV)

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Valentina Valenzuela-Muñoz ◽  
Patricia Pereiro ◽  
Margarita Álvarez-Rodríguez ◽  
Cristian Gallardo-Escárate ◽  
Antonio Figueras ◽  
...  

Abstract Although the modulation of immune-related genes after viral infection has been widely described in vertebrates, the potential implications of non-coding RNAs (ncRNAs), especially long non-coding RNAs (lncRNAs), in immunity are still a nascent research field. The model species zebrafish could serve as a useful organism for studying the functionality of lncRNAs due to the numerous advantages of this teleost, including the existence of numerous mutant lines. In this work, we conducted a whole-transcriptome analysis of wild-type (WT) and heterozygous rag1 mutant (rag1+/−) zebrafish after infection with the pathogen spring viraemia of carp virus (SVCV). WT and rag1+/− zebrafish were infected with SVCV for 24 h. Kidney samples were sampled from infected and uninfected fish for transcriptome sequencing. From a total of 198,540 contigs, 12,165 putative lncRNAs were identified in zebrafish. Most of the putative lncRNAs were shared by the two zebrafish lines. However, by comparing the lncRNA profiles induced after SVCV infection in WT and rag1+/− fish, most of the lncRNAs that were significantly induced after viral challenge were exclusive to each line, reflecting a highly differential response to the virus. Analysis of the neighboring genes of lncRNAs that were exclusively modulated in WT revealed high representation of metabolism-related terms, whereas those from rag1+/− fish showed enrichment in terms related to the adaptive immune response, among others. On the other hand, genes involved in numerous antiviral processes surrounded commonly modulated lncRNAs, as expected. These results clearly indicate that after SVCV infection in zebrafish, the expression of an array of lncRNAs with functions in different aspects of immunity is induced.

Author(s):  
Lang Xie ◽  
Zheyu Chen ◽  
Hui Guo ◽  
Yixi Tao ◽  
Xiaomin Miao ◽  
...  

Splenectomy or congenital asplenia in humans increases susceptibility to infections. We have previously reported that congenital asplenia in zebrafish reduces resistance to Aeromonas hydrophila infection. However, the molecular mechanism of systemic immune response in congenitally asplenic individuals is largely unexplored. In this study, we found that pro-inflammatory cytokines were more highly induced in congenitally asplenic zebrafish than wild-type after pathogenic A. hydrophila infection and lipopolysaccharide exposure. In addition, a higher aggregation of apoptotic cells was observed in congenitally asplenic zebrafish than that in wild-type. Next, we examined the transcriptome profiles of whole kidneys from wild-type and congenitally asplenic zebrafish to investigate the effects of congenital asplenia on innate and adaptive immune responses induced by the inactivated A. hydrophila. Congenital asplenia inactivated the splenic anti-inflammatory reflex, disrupted immune homeostasis, and induced excessive inflammation as evidenced by the highly induced stress response–related biological processes, inflammatory and apoptosis-associated pathways, and pro-inflammatory cytokines/chemokines in congenitally asplenic zebrafish compared with wild-type after vaccination. In addition, complement component genes (c3a.1, c3a.6, c4, c6, and c9) and several important immune-related genes (tabp.1, tap1, hamp, prg4b, nfil3, defbl1, psmb9a, tfr1a, and sae1) were downregulated in congenitally asplenic zebrafish. Furthermore, congenital asplenia impaired adaptive immunity as demonstrated by downregulation of biological processes and signaling pathways involved in adaptive immune response after vaccination in congenitally asplenic zebrafish. The expression of MHCII/IgM was also significantly reduced in the congenitally asplenic zebrafish when compared with wild-type. Together, our study provides an in-depth understanding of spleen function in controlling immune homeostasis and may offer insight into the pathological response in splenectomized or congenitally asplenic patients after infections.


2021 ◽  
Author(s):  
Xiaopeng An ◽  
Yue Zhang ◽  
Fu Li ◽  
Zhanhang Wang ◽  
Shaohua Yang ◽  
...  

Abstract BackgroundEstrous cycle is one of female characteristics after sexual maturity, including estrus (ES) and diestrus (DS) stages. Estrous cycle is important in female physiology and its disorder may lead to diseases. In the latest years, effects of non-coding RNAs and mRNA on estrous cycle start to arouse much concern, however, a whole transcriptome analysis among non-coding RNAs and mRNA has not been reported.ResultsHere we report a whole transcriptome analysis of goat ovary in estrus and diestrus periods. Estrus synchronization was conducted to induce the estrus phase and on day 32, the goats naturally shifted into diestrus stage. The ovary RNA of estrus and diestrus stages was respectively collected to perform RNA-sequencing. Then the circular RNA; microRNA; long non-coding RNA; mRNA databases of goat ovary were acquired, and the differentially expressions between estrus and diestrus stages were screened to construct circRNA-miRNA-mRNA/lncRNA and lncRNA-miRNA/mRNA networks, thus providing potential pathways that involved in the regulation of estrous cycle. Differentially expressed mRNAs, such as MMP9, TIMP1, 3BHSD and PTGIS, and differentially expressed microRNAs, such as miR-21-3p,miR-202-3p and miR-223-3p, which play key roles in estrous cycle regulation were extracted from the network.ConclusionsOur data provided the miRNA, circRNA, lncRNA and mRNA databases of goat ovary and each differentially expressed profile between ES and DS. Networks among differentially expressed miRNAs, circRNAs, lncRNAs and mRNAs were constructed to provide valuable resources for the study of estrous cycle and related diseases.


1999 ◽  
Vol 67 (4) ◽  
pp. 2001-2004 ◽  
Author(s):  
Sing Sing Way ◽  
Alain C. Borczuk ◽  
Marcia B. Goldberg

ABSTRACT Shigella flexneri cydC, which is deficient in cytochrome bd, was rapidly cleared from the lungs of intranasally inoculated mice and was Sereny negative, yet it induced 93% protection against challenge with wild-type S. flexneri. Mice that lack immunoglobulin A (IgA) were fully protected, suggesting that IgA may not be required for adaptive immunity in this model system.


2014 ◽  
Vol 5 (3) ◽  
pp. 235-246 ◽  
Author(s):  
G. Pérez Martínez ◽  
C. Bäuerl ◽  
M.C. Collado

Today, advances in the public health system of most countries have managed to extend notably life expectancy, however, elderly's health remain as a very serious concern. The lifelong stimulation of innate and adaptive immune systems leads to immunosenescence and, as result, to a low ability to produce immunoglobulins against pathogens but also to a low-grade chronic inflammatory state (inflammaging) that is linked to most age-related health problems, such as dementia, Alzheimer or atherosclerosis. This inflammatory state could make the host more sensitive to intestinal microbes, or vice versa, as changes in the gut microbiota composition are related to the progression of diseases and frailty in the elderly population. It was considered that gut microbiota changed during aging, with an increase of Bacteroidetes vs. Firmicutes proportion and a reduction of bifidobacterial counts, however recent studies reported a great inter-individual variation among elderly and a significant relationship between gut microbiota, diet and institution or community living. Intervention studies of probiotics and prebiotics in elderly are not very abundant, but most cases showed that Bifidobacterium populations can efficiently be stimulated with a concomitant decrease of Enterobacteria. Furthermore, also some studies demonstrated that probiotics decreased the synthesis of pro-inflammatory cytokines which are upregulated in the elderly, such as interleukin (IL)-8, IL-6 or tumour necrosis factor ?, among others, and they increased the levels of activated lymphocytes, natural killer cells, phagocytic activity and even showed a greater response to influenza vaccination. This suggests that direct manipulation of the gut microbiota may improve adaptive immune response and reduce inflammatory secretions, therefore compensating immunosenescence effects, however, there are no records of their effect on clinical symptoms or risk for disease. Those facts reveal that this is an open research field with very good scientific perspectives and above all they could bring likely improvements in the wellbeing of our seniors.


2006 ◽  
Vol 74 (10) ◽  
pp. 5730-5738 ◽  
Author(s):  
Ann Marie Galioto ◽  
Jessica A. Hess ◽  
Thomas J. Nolan ◽  
Gerhard A. Schad ◽  
James J. Lee ◽  
...  

ABSTRACT The goal of this study was to determine the roles of eosinophils and neutrophils in innate and adaptive protective immunity to larval Strongyloides stercoralis in mice. The experimental approach used was to treat mice with an anti-CCR3 monoclonal antibody to eliminate eosinophils or to use CXCR2−/− mice, which have a severe neutrophil recruitment defect, and then determine the effect of the reduction or elimination of the particular cell type on larval killing. It was determined that eosinophils killed the S. stercoralis larvae in naïve mice, whereas these cells were not required for the accelerated killing of larvae in immunized mice. Experiments using CXCR2−/− mice demonstrated that the reduction in recruitment of neutrophils resulted in significantly reduced innate and adaptive protective immunity. Protective antibody developed in the immunized CXCR2−/− mice, thereby demonstrating that neutrophils were not required for the induction of the adaptive protective immune response. Moreover, transfer of neutrophil-enriched cell populations recovered from either wild-type or CXCR2−/− mice into diffusion chambers containing larvae demonstrated that larval killing occurred with both cell populations when the diffusion chambers were implanted in immunized wild-type mice. Thus, the defect in the CXCR2−/− mice was a defect in the recruitment of the neutrophils and not a defect in the ability of these cells to kill larvae. This study therefore demonstrated that both eosinophils and neutrophils are required in the protective innate immune response, whereas only neutrophils are necessary for the protective adaptive immune response to larval S. stercoralis in mice.


2016 ◽  
Vol 85 (1) ◽  
Author(s):  
Wiebke Theeß ◽  
Julie Sellau ◽  
Christiane Steeg ◽  
Anna Klinke ◽  
Stephan Baldus ◽  
...  

ABSTRACT Myeloperoxidase (MPO), a leukocyte-derived enzyme mainly secreted by activated neutrophils, is known to be involved in the immune response during bacterial and fungal infection and inflammatory diseases. Nevertheless, the role of MPO in a parasitic disease like malaria is unknown. We hypothesized that MPO contributes to parasite clearance. To address this hypothesis, we used Plasmodium yoelii nonlethal infection in wild-type and MPO-deficient mice as a murine malaria model. We detected high MPO plasma levels in wild-type mice with Plasmodium yoelii infection. Unexpectedly, infected MPO-deficient mice did not show increased parasite loads but were able to clear the infection more rapidly than wild-type mice. Additionally, the presence of neutrophils at the onset of infection seemed not to be essential for the control of the parasitemia. The effect of decreased parasite levels in MPO-deficient mice was absent from animals lacking mature T and B cells, indicating that this effect is most likely dependent on adaptive immune response mechanisms. Indeed, we observed increased gamma interferon and tumor necrosis factor alpha production by T cells in infected MPO-deficient mice. Together, these results suggest that MPO modulates the adaptive immune response during malaria infection, leading to an attenuated parasite clearance.


2010 ◽  
Vol 78 (7) ◽  
pp. 3019-3026 ◽  
Author(s):  
Amanda J. Read ◽  
Sara Erickson ◽  
Allen G. Harmsen

ABSTRACT The mechanisms of the primary adaptive immune response to Coxiella burnetii are not well known. Following inoculation of the lungs with C. burnetii Nine Mile phase I (NMI), SCID mice developed pneumonia and splenomegaly and succumbed to infection, whereas wild-type mice cleared the infection by 24 days. SCID mice reconstituted with either CD4+ T cells or CD8+ T cells alone were able to control the infection, indicating that the presence of either type of T cells was sufficient to control infection, and B cells were not necessary for primary immunity. Similarly, wild-type mice depleted of either CD4+ T cells or CD8+ T cells controlled infections in their lungs, but these mice were highly susceptible if they were depleted of both types of T cells. However, compared to CD4+ T-cell-dependent protection, CD8+ T-cell-dependent protection resulted in less inflammation in the lungs and less growth of bacteria in the spleens.


Biology ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 464
Author(s):  
Xiaopeng An ◽  
Yue Zhang ◽  
Fu Li ◽  
Zhanhang Wang ◽  
Shaohua Yang ◽  
...  

Estrous cycle is one of the placental mammal characteristics after sexual maturity, including estrus stage (ES) and diestrus stage (DS). Estrous cycle is important in female physiology and its disorder may lead to diseases, such as polycystic ovary syndrome, ovarian carcinoma, anxiety, and epilepsy. In the latest years, effects of non-coding RNAs and messenger RNA (mRNA) on estrous cycle have started to arouse much concern, however, a whole transcriptome analysis among non-coding RNAs and mRNA has not been reported. Here, we report a whole transcriptome analysis of goat ovary in estrus and diestrus periods. Estrus synchronization was conducted to induce the estrus phase and on day 32, the goats shifted into the diestrus stage. The ovary RNA of estrus and diestrus stages was respectively collected to perform RNA-sequencing. Then, the circular RNA (circRNA), microRNA (miRNA), long non-coding RNA (lncRNA), and mRNA databases of goat ovary were acquired, and the differential expressions between estrus and diestrus stages were screened to construct circRNA-miRNA-mRNA/lncRNA and lncRNA-miRNA/mRNA networks, thus providing potential pathways that are involved in the regulation of estrous cycle. Differentially expressed mRNAs, such as MMP9, TIMP1, 3BHSD, and PTGIS, and differentially expressed miRNAs that play key roles in the regulation of estrous cycle, such as miR-21-3p, miR-202-3p, and miR-223-3p, were extracted from the network. Our data provided the miRNA, circRNA, lncRNA, and mRNA databases of goat ovary and each differentially expressed profile between ES and DS. Networks among differentially expressed miRNAs, circRNAs, lncRNAs, and mRNAs were constructed to provide valuable resources for the study of estrous cycle and related diseases.


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