scholarly journals Congenital Asplenia Interrupts Immune Homeostasis and Leads to Excessive Systemic Inflammation in Zebrafish

2021 ◽  
Vol 11 ◽  
Author(s):  
Lang Xie ◽  
Zheyu Chen ◽  
Hui Guo ◽  
Yixi Tao ◽  
Xiaomin Miao ◽  
...  
Keyword(s):  
Immune Response ◽  
Inflammatory Cytokines ◽  
Adaptive Immune Response ◽  
Immune Homeostasis ◽  
Biological Processes ◽  
Wild Type ◽  
Adaptive Immune ◽  
Immune Related Genes ◽  
Insight Into ◽  
Pro Inflammatory Cytokines

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.

scholarly journals Adaptive Immune Response to Shigella flexneri 2acydC in Immunocompetent Mice and Mice Lacking Immunoglobulin A

1999 ◽  
Vol 67 (4) ◽  
pp. 2001-2004 ◽  
Author(s):  
Sing Sing Way ◽  
Alain C. Borczuk ◽  
Marcia B. Goldberg
Keyword(s):  
Immune Response ◽  
Adaptive Immunity ◽  
Shigella Flexneri ◽  
Immunoglobulin A ◽  
Adaptive Immune Response ◽  
Model System ◽  
Wild Type ◽  
Adaptive Immune ◽  
Immunocompetent Mice

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.

scholarly journals Role of Eosinophils and Neutrophils in Innate and Adaptive Protective Immunity to Larval Strongyloides stercoralis in Mice

2006 ◽  
Vol 74 (10) ◽  
pp. 5730-5738 ◽  
Author(s):  
Ann Marie Galioto ◽  
Jessica A. Hess ◽  
Thomas J. Nolan ◽  
Gerhard A. Schad ◽  
James J. Lee ◽  
...  
Keyword(s):  
Immune Response ◽  
Protective Immunity ◽  
Experimental Approach ◽  
Adaptive Immune Response ◽  
Strongyloides Stercoralis ◽  
Cell Populations ◽  
Wild Type ◽  
Diffusion Chambers ◽  
Adaptive Immune

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.

scholarly journals Bioorthogonal Protein Labelling Enables The Study Of Antigen Processing of Citrullinated and Carbamylated Auto-Antigens

2021 ◽  
Author(s):  
Tyrza van Leeuwen ◽  
Can Araman ◽  
Linda Pieper Pournara ◽  
Arieke S.B. Kampstra ◽  
Thomas Bakkum ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Antigen Processing ◽  
Adaptive Immune Response ◽  
Short Peptides ◽  
Biological Processes ◽  
Protein Labelling ◽  
Adaptive Immune ◽  
Antigenic Material

Proteolysis is fundamental to many biological processes. In the immune system, it underpins the activation of the adaptive immune response: degradation of antigenic material into short peptides and presentation thereof...

scholarly journals Antigen Capture of Porphyromonas gingivalis by Human Macrophages Is Enhanced but Killing and Antigen Presentation Are Reduced by Endotoxin Tolerance

2007 ◽  
Vol 76 (2) ◽  
pp. 477-485 ◽  
Author(s):  
Manoj Muthukuru ◽  
Christopher W. Cutler
Keyword(s):  
Immune Response ◽  
Cell Proliferation ◽  
Porphyromonas Gingivalis ◽  
Inflammatory Cytokines ◽  
Adaptive Immune Response ◽  
Endotoxin Tolerance ◽  
Costimulatory Molecules ◽  
T Cell Proliferation ◽  
Human Macrophages ◽  
Adaptive Immune

ABSTRACT The innate and the adaptive arms of the mucosal immune system must be coordinated to facilitate the control of pathogenic invasion while maintaining immune homeostasis. Toll-like receptors, able to activate the cell to produce bactericidal and inflammatory cytokines but also able to upregulate antigen (Ag)-presenting and costimulatory molecules, are particularly important in this regard. We have previously shown that the chronically infected oral mucosa is in a state of endotoxin tolerance, as evidenced by the downregulation of Toll-like receptors 2 and 4 and of inflammatory cytokines and the upregulation of SH2-containing inositol phosphatase, an inhibitor of NF-κB signaling. In the present study, we hypothesized that endotoxin tolerance would influence the ability of human macrophages to engage in Ag capture and killing of the oral pathogen Porphyromonas gingivalis and to upregulate costimulatory molecules and stimulate autologous T-cell proliferation. We show that uptake, but not killing, of P. gingivalis 381 is enhanced by endotoxin tolerance. Reduced killing is possibly due to a reduction of the intracellular lysosomes. We further show that the expression of the Ag-presenting molecule HLA-DR and costimulatory molecules CD40 and CD86 is dampened by endotoxin tolerance to the constitutive level. This, along with our previous evidence for reduction in immunostimulatory cytokines, is consistent with the observed decrease in the induction of autologous CD4+ T-cell proliferation by endotoxin-tolerized macrophages. Overall, these studies suggest that endotoxin tolerance, as observed in the inflamed oral mucosa, potentiates the innate Ag capture activity of macrophages but diminishes the potential of human macrophages to initiate the adaptive immune response. In conclusion, endotoxin tolerance, while helpful in bacterial clearance and in surmounting excessive inflammatory tissue damage, could potentially reduce the (protective) adaptive immune response during chronic infections such as periodontitis.

scholarly journals Inflammasomes and SARS-CoV-2 Infection

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2513
Author(s):  
Juha Kaivola ◽  
Tuula Anneli Nyman ◽  
Sampsa Matikainen
Keyword(s):  
Immune Response ◽  
Inflammatory Cytokines ◽  
Influenza A ◽  
Protein Complexes ◽  
Severe Disease ◽  
Adaptive Immune Response ◽  
Innate Immune ◽  
Multiple Organs ◽  
New Type ◽  
Pro Inflammatory Cytokines

SARS-CoV-2 is a new type of coronavirus that has caused worldwide pandemic. The disease induced by SARS-CoV-2 is called COVID-19. A majority of people with COVID-19 have relatively mild respiratory symptoms. However, a small percentage of COVID-19 patients develop a severe disease where multiple organs are affected. These severe forms of SARS-CoV-2 infections are associated with excessive production of pro-inflammatory cytokines, so called “cytokine storm”. Inflammasomes, which are protein complexes of the innate immune system orchestrate development of local and systemic inflammation during virus infection. Recent data suggest involvement of inflammasomes in severe COVID-19. Activation of inflammasome exerts two major effects: it activates caspase-1-mediated processing and secretion of pro-inflammatory cytokines IL-1β and IL-18, and induces inflammatory cell death, pyroptosis, via protein called gasdermin D. Here, we provide comprehensive review of current understanding of the activation and possible functions of different inflammasome structures during SARS-CoV-2 infection and compare that to response caused by influenza A virus. We also discuss how novel SARS-CoV-2 mRNA vaccines activate innate immune response, which is a prerequisite for the activation of protective adaptive immune response.

scholarly journals Bioorthogonal antigens allow the unbiased study of antigen processing and presentation

2018 ◽  
Author(s):  
Can Araman ◽  
Linda Pieper-Pournara ◽  
Tyrza van Leeuwen ◽  
Arieke S. B. Kampstra ◽  
Thomas Bakkum ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune System ◽  
Antigen Processing ◽  
Adaptive Immune Response ◽  
Short Peptides ◽  
Biological Processes ◽  
Adaptive Immune ◽  
Major Histocompatibility Complexes ◽  
Antigenic Material ◽  
Antigen Processing And Presentation

AbstractProteolysis is fundamental to many biological processes. In the immune system, it underpins the activation of the adaptive immune response: degradation of antigenic material into short peptides and presentation thereof on major histocompatibility complexes, leads to activation of T-cells. This initiates the adaptive immune response against many pathogens.

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 ◽  
...  
Keyword(s):  
Adaptive Immune Response ◽  
Research Field ◽  
Wild Type ◽  
Adaptive Immune ◽  
Non Coding Rnas ◽  
Whole Transcriptome Analysis ◽  
Immune Related Genes ◽  
Mutant Lines ◽  
Whole Transcriptome ◽  
High Representation

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.

scholarly journals Robust Virus-Specific Adaptive Immunity in COVID-19 Patients with SARS-CoV-2 Δ382 Variant Infection

2021 ◽  
Author(s):  
Siew-Wai Fong ◽  
Nicholas Kim-Wah Yeo ◽  
Yi-Hao Chan ◽  
Yun Shan Goh ◽  
Siti Naqiah Amrun ◽  
...  
Keyword(s):  
T Cell ◽  
Adaptive Immune Response ◽  
Initiation Factor ◽  
Great Promise ◽  
Adaptive Immune ◽  
Cell Immunity ◽  
Initiation Factor 2 ◽  
Cell Functionality ◽  
Insight Into ◽  
Pro Inflammatory Cytokines

Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VOCs) that have become dominant as the pandemic progresses bear the ORF8 mutation together with multiple spike mutations. A 382-nucleotide deletion (Δ382) in the ORF7b and ORF8 regions has been associated with milder disease phenotype and less systemic inflammation in COVID-19 patients. However, its impact on host immunity against SARS-CoV-2 remains undefined. Here, RNA-sequencing was performed to elucidate whole blood transcriptomic profiles and identify contrasting immune signatures between patients infected with either wildtype or Δ382 SARS-CoV-2 variant. Interestingly, the immune landscape of Δ382 SARS-CoV-2 infected patients featured an increased adaptive immune response, evidenced by enrichment of genes related to T cell functionality, a more robust SARS-CoV-2-specific T cell immunity, as well as a more rapid antibody response. At the molecular level, eukaryotic initiation factor 2 signaling was found to be upregulated in patients bearing Δ382, and its associated genes were correlated with systemic levels of T cell-associated and pro-inflammatory cytokines. This study provides more in-depth insight into the host–pathogen interactions of ORF8 with great promise as a therapeutic target to combat SARS-CoV-2 infection.

scholarly journals Myeloperoxidase Attenuates Pathogen Clearance during Plasmodium yoelii Nonlethal Infection

2016 ◽  
Vol 85 (1) ◽  
Author(s):  
Wiebke Theeß ◽  
Julie Sellau ◽  
Christiane Steeg ◽  
Anna Klinke ◽  
Stephan Baldus ◽  
...  
Keyword(s):  
Immune Response ◽  
Inflammatory Diseases ◽  
Adaptive Immune Response ◽  
Parasite Clearance ◽  
Plasmodium Yoelii ◽  
Wild Type ◽  
Necrosis Factor Alpha ◽  
Content Type ◽  
Adaptive Immune ◽  
Deficient Mice

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.

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