In vitro and in vivo roles in Collectin Kidney 1 (CL-K1) with innate immunity against Streptococcus pneumoniae

Immunobiology ◽  
2016 ◽  
Vol 221 (10) ◽  
pp. 1217 ◽  
Author(s):  
Insu Hwang ◽  
Kenichiro Mori ◽  
Katsuki Ohtani ◽  
Yasuyuki Matsuda ◽  
Nitai Roy ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Streptococcus Pneumoniae

scholarly journals Collectin Kidney 1 Plays an Important Role in Innate Immunity against Streptococcus pneumoniae Infection

2017 ◽  
Vol 9 (2) ◽  
pp. 217-228 ◽  
Author(s):  
Insu Hwang ◽  
Kenichiro Mori ◽  
Katsuki Ohtani ◽  
Yasuyuki Matsuda ◽  
Nitai Roy ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Streptococcus Pneumoniae ◽  
Pulmonary Inflammation ◽  
Dependent Manner ◽  
Complement Pathway ◽  
Calcium Dependent ◽  
Host Protection ◽  
In The Wild

Collectins are C-type lectins that are involved in innate immunity as pattern recognition molecules. Recently, collectin kidney 1 (CL-K1) has been discovered, and in vitro studies have shown that CL-K1 binds to microbes and activates the lectin complement pathway. However, in vivo functions of CL-K1 against microbes have not been elucidated. To investigate the biological functions of CL-K1, we generated CL-K1 knockout (CL-K1-/-) mice and then performed a Streptococcus pneumoniae infection analysis. First, we found that recombinant human CL-K1 bound to S. pneumoniae in a calcium-dependent manner, and induced complement activation. CL-K1-/- mice sera formed less C3 deposition on S. pneumoniae. Furthermore, immunofluorescence analysis in the wild-type (WT) mice demonstrated that CL-K1 and C3 were localized on S. pneumoniae in infected lungs. CL-K1-/- mice revealed decreased phagocytosis of S. pneumoniae. Consequently, less S. pneumoniae clearance was observed in their lungs. CL-K1-/- mice showed severe pulmonary inflammation and weight loss in comparison with WT mice. Finally, the decreased clearance and severe pulmonary inflammation caused by S. pneumoniae infection might cause higher CL-K1-/- mice lethality. Our results suggest that CL-K1 might play an important role in host protection against S. pneumoniae infection through the activation of the lectin complement pathway.

scholarly journals In vitro and in vivo evaluation of virus-induced innate immunity in mouse

2021 ◽  
Vol 2 (3) ◽  
pp. 100708
Author(s):  
Long Shen ◽  
Xiao Shan ◽  
Penghui Hu ◽  
Yanan Zhang ◽  
Zemin Ji ◽  
...  
Keyword(s):  
Innate Immunity ◽  
In Vivo Evaluation

scholarly journals In Vitro and In Vivo Activities of DA-7867, a New Oxazolidinone, against Aerobic Gram-Positive Bacteria

2005 ◽  
Vol 49 (6) ◽  
pp. 2498-2500 ◽  
Author(s):  
Eun Jeong Yoon ◽  
Yeong Woo Jo ◽  
Sung Hak Choi ◽  
Tae Ho Lee ◽  
Jae Keol Rhee ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Streptococcus Pneumoniae ◽  
Gram Positive ◽  
Methicillin Resistant ◽  
Gram Positive Bacteria ◽  
Vancomycin Resistant Enterococci ◽  
Infection Models ◽  
Vancomycin Resistant

ABSTRACT In vitro and in vivo activities of DA-7867 were assessed against methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, and penicillin-resistant Streptococcus pneumoniae. All isolates were inhibited by DA-7867 at ≤0.78 μg/ml, a four-times-lower concentration than that of inhibition by linezolid. For murine infection models, DA-7867 also exhibited greater efficacy than linezolid against all isolates tested.

scholarly journals Virulent Shigella flexneri subverts the host innate immune response through manipulation of antimicrobial peptide gene expression

2008 ◽  
Vol 205 (5) ◽  
pp. 1121-1132 ◽  
Author(s):  
Brice Sperandio ◽  
Béatrice Regnault ◽  
Jianhua Guo ◽  
Zhi Zhang ◽  
Samuel L. Stanley ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Shigella Flexneri ◽  
Host Cells ◽  
Virulence Plasmid ◽  
Cationic Peptides ◽  
Immunity Genes ◽  
Genes Encoding ◽  
Peptide Gene

Antimicrobial factors are efficient defense components of the innate immunity, playing a crucial role in the intestinal homeostasis and protection against pathogens. In this study, we report that upon infection of polarized human intestinal cells in vitro, virulent Shigella flexneri suppress transcription of several genes encoding antimicrobial cationic peptides, particularly the human β-defensin hBD-3, which we show to be especially active against S. flexneri. This is an example of targeted survival strategy. We also identify the MxiE bacterial regulator, which controls a regulon encompassing a set of virulence plasmid-encoded effectors injected into host cells and regulating innate signaling, as being responsible for this dedicated regulatory process. In vivo, in a model of human intestinal xenotransplant, we confirm at the transcriptional and translational level, the presence of a dedicated MxiE-dependent system allowing S. flexneri to suppress expression of antimicrobial cationic peptides and promoting its deeper progression toward intestinal crypts. We demonstrate that this system is also able to down-regulate additional innate immunity genes, such as the chemokine CCL20 gene, leading to compromised recruitment of dendritic cells to the lamina propria of infected tissues. Thus, S. flexneri has developed a dedicated strategy to weaken the innate immunity to manage its survival and colonization ability in the intestine.

scholarly journals Coronavirus Infection and BCG Vaccination: Facts and Possibilities

2020 ◽  
Vol 19 (5) ◽  
pp. 18-24
Author(s):  
B. V. Karalnik ◽  
B. I. Alimbekova ◽  
L. T. Eralieva
Keyword(s):  
Innate Immunity ◽  
Risk Groups ◽  
Optimal Timing ◽  
Scientific Publications ◽  
Bcg Vaccination ◽  
Outbreak Period ◽  
Vaccine Prophylaxis ◽  
Scientific Facts

Relevance. The relevance of protection against SARS-Cov-19 by means of BCG vaccination is important not only with respect to coronavirus infections. That issue should be considered in light of overall biological and immunological pillars (innate immunity system).Aims. To consider the role of the lipid components and certain vaccines in stimulation of the innate immunity system, in particular, in induction of the heterogenous immune response and protection against various pathogens, including Covid-19, based on analysis of known scientific facts.Conclusions. The relevant database has been analyzed (51 scientific publications), including studies with application of various methods from immunological tests (in vitro and in vivo) to epidemiological trials. The analysis revealed the meaningful potential of heterogenous protection against various infections by means of BCG immunization, and according to some data, measles vaccine capacity. Simultaneously on the basis of performed analysis, the following issues that so far remained unclear have been identified: what is the duration of heterogenous protection; what is the optimal timing for BCG administration as related to the outbreak period of dangerous infection for the sake of decrease of its harm. The analyzed materials of that review substantiate the rationale for further continuation of the scientific studies and possibility for application of already accumulated data in order to protect, primarily the risk groups, against dangerous infections, especially in the timeframe when no relevant vaccines are available. Besides, the conducted review serves as the leverage for expected development of the new preventive medicine dimension – the systemic vaccine prophylaxis.

scholarly journals Characterization of the Anti-Inflammatory Capacity of IL-10-Producing Neutrophils in Response to Streptococcus pneumoniae Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Liliana A. González ◽  
Felipe Melo-González ◽  
Valentina P. Sebastián ◽  
Omar P. Vallejos ◽  
Loreani P. Noguera ◽  
...  
Keyword(s):  
Streptococcus Pneumoniae ◽  
Lung Injury ◽  
Interleukin 10 ◽  
Effector Cells ◽  
Cellular Source ◽  
Lung Histopathology ◽  
Morphological Differences ◽  
Direct Recognition

Neutrophils are immune cells classically defined as pro-inflammatory effector cells. However, current accumulated evidence indicates that neutrophils have more versatile immune-modulating properties. During acute lung infection with Streptococcus pneumoniae in mice, interleukin-10 (IL-10) production is required to temper an excessive lung injury and to improve survival, yet the cellular source of IL-10 and the immunomodulatory role of neutrophils during S. pneumoniae infection remain unknown. Here we show that neutrophils are the main myeloid cells that produce IL-10 in the lungs during the first 48 h of infection. Importantly, in vitro assays with bone-marrow derived neutrophils confirmed that IL-10 can be induced by these cells by the direct recognition of pneumococcal antigens. In vivo, we identified the recruitment of two neutrophil subpopulations in the lungs following infection, which exhibited clear morphological differences and a distinctive profile of IL-10 production at 48 h post-infection. Furthermore, adoptive transfer of neutrophils from WT mice into IL-10 knockout mice (Il10-/-) fully restored IL-10 production in the lungs and reduced lung histopathology. These results suggest that IL-10 production by neutrophils induced by S. pneumoniae limits lung injury and is important to mediate an effective immune response required for host survival.

scholarly journals Synthetic gene regulatory networks in the opportunistic human pathogen Streptococcus pneumoniae

2019 ◽  
Author(s):  
Robin A. Sorg ◽  
Clement Gallay ◽  
Jan-Willem Veening
Keyword(s):  
Gene Expression ◽  
Streptococcus Pneumoniae ◽  
Regulatory Networks ◽  
Expression Patterns ◽  
Combinatorial Libraries ◽  
Regulatory Elements ◽  
Expression Control ◽  
Gene Expression Control

AbstractStreptococcus pneumoniae can cause disease in various human tissues and organs, including the ear, the brain, the blood and the lung, and thus in highly diverse and dynamic environments. It is challenging to study how pneumococci control virulence factor expression, because cues of natural environments and the presence of an immune system are difficult to simulate in vitro. Here, we apply synthetic biology methods to reverse-engineer gene expression control in S. pneumoniae. A selection platform is described that allows for straightforward identification of transcriptional regulatory elements out of combinatorial libraries. We present TetR- and LacI-regulated promoters that show expression ranges of four orders of magnitude. Based on these promoters, regulatory networks of higher complexity are assembled, such as logic AND and IMPLY gates. Finally, we demonstrate single-copy genome-integrated toggle switches that give rise to bimodal population distributions. The tools described here can be used to mimic complex expression patterns, such as the ones found for pneumococcal virulence factors, paving the way for in vivo investigations of the importance of gene expression control on the pathogenicity of S. pneumoniae.

scholarly journals Mechanism of innate immune reprogramming by a fungal meningitis pathogen

2021 ◽  
Author(s):  
Eric V. Dang ◽  
Susan Lei ◽  
Atanas Radkov ◽  
Hiten Madhani
Keyword(s):  
Innate Immunity ◽  
Fungal Pathogens ◽  
Forward Genetics ◽  
Alternative Activation ◽  
Cytokine Signaling ◽  
Alternatively Activated Macrophages ◽  
Fungal Meningitis

How deadly fungal pathogens overcome mammalian innate immunity is largely unknown. Cryptococcus neoformans, the most common cause of fungal meningitis, induces a pathogenic type 2 response characterized by pulmonary eosinophilia and alternatively activated macrophages. Using forward genetics, we identified a fungal secreted protein, Cpl1, necessary and sufficient to enhance alternative activation of primary macrophages in vitro. Cpl1-enhanced polarization requires Toll-like receptor 4, a known mediator of allergen-induced type 2 responses. Cpl1 is essential for virulence, drives polarization of interstitial macrophages in vivo, and requires type 2 cytokine signaling for its impact on infectivity. C. neoformans selectively associates with polarized interstitial macrophages during infection, supporting a direct host-pathogen interaction. This work identifies a secreted effector produced by a human fungal pathogen that reprograms innate immunity to enable tissue infection.

scholarly journals Draft Genome Sequence of Pediatric Otitis Media Isolate Streptococcus pneumoniae Strain EF3030, Which Forms In Vitro Biofilms That Closely Mimic In Vivo Biofilms

2019 ◽  
Vol 8 (2) ◽  
Author(s):  
Edgar J. Scott ◽  
Nicole R. Luke-Marshall ◽  
Anthony A. Campagnari ◽  
David W. Dyer
Keyword(s):  
Streptococcus Pneumoniae ◽  
Otitis Media ◽  
Genome Sequence ◽  
Dna Sequences ◽  
Draft Genome ◽  
Draft Genome Sequence ◽  
Draft Assembly ◽  
Content Type

Here, we report the draft genome sequence of Streptococcus pneumoniae EF3030, a pediatric otitis media isolate active in biofilm assays of epithelial colonization. The final draft assembly included 2,209,198 bp; the annotation predicted 2,120 coding DNA sequences (CDSs), 4 complete rRNA operons, 58 tRNAs, 3 noncoding RNAs (ncRNAs), and 199 pseudogenes.

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