scholarly journals Complex Involvement of Interleukin-26 in Bacterial Lung Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Karlhans F. Che ◽  
Magnus Paulsson ◽  
Krzysztof Piersiala ◽  
Jakob Sax ◽  
Ibrahim Mboob ◽  
...  
Keyword(s):  
Klebsiella Pneumoniae ◽  
Immune Responses ◽  
Therapeutic Potential ◽  
Ex Vivo ◽  
Lung Infection ◽  
Innate Immune ◽  
Alveolar Epithelial Cells ◽  
Lower Airway ◽  
Innate Immune Responses ◽  
Human Lung Tissue

Pneumonia is a global cause of mortality, and this provides a strong incentive to improve the mechanistic understanding of innate immune responses in the lungs. Here, we characterized the involvement of the cytokine interleukin (IL)-26 in bacterial lung infection. We observed markedly increased concentrations of IL-26 in lower airway samples from patients with bacterial pneumonia and these correlated with blood neutrophil concentrations. Moreover, pathogen-associated molecular patterns (PAMPs) from both Gram-negative and -positive bacteria increased extracellular IL-26 concentrations in conditioned media from human models of alveolar epithelial cells, macrophages, and neutrophils in vitro. Stimulation with IL-26 inhibited the inherent release of neutrophil elastase and myeloperoxidase in unexposed neutrophils. This stimulation also inhibited the expression of activity makers in neutrophils exposed to Klebsiella pneumoniae. In addition, priming of human lung tissue ex vivo with exogenous IL-26 potentiated the endotoxin-induced increase in mRNA for other cytokines involved in the innate immune response, including the master Th17-regulator IL-23 and the archetype inhibitory cytokine IL-10. Finally, neutralization of endogenous IL-26 clearly increased the growth of Klebsiella pneumoniae in the macrophage culture. These findings suggest that IL-26 is involved in bacterial lung infection in a complex manner, by modulating critical aspects of innate immune responses locally and systemically in a seemingly purposeful manner and by contributing to the killing of bacteria in a way that resembles an antimicrobial peptide. Thus, IL-26 displays both diagnostic and therapeutic potential in pneumonia and deserves to be further evaluated in these respects.

scholarly journals Integrated role of microRNA-30e-5p through targeting negative regulators of innate immune pathways during HBV infection and SLE

2020 ◽  
Author(s):  
Richa Mishra ◽  
Sanjana Bhattacharya ◽  
Bhupendra S Rawat ◽  
Ashish Kumar ◽  
Akhilesh Kumar ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Mouse Model ◽  
Immune Responses ◽  
Therapeutic Potential ◽  
Innate Immune ◽  
Locked Nucleic Acid ◽  
Type I ◽  
Innate Immune Responses ◽  
Negative Regulators

AbstractPrecise regulation of innate immunity is crucial for the development of appropriate host immunity against microbial infections and the maintenance of immune homeostasis. The microRNAs are small non-coding RNA, post-transcriptional regulator of multiple genes and act as a rheostat for protein expression. Here, we identified microRNA(miR)-30e-5p (miR-30e) induced by the hepatitis B virus (HBV) and other viruses that act as a master regulator for innate immune responses. Moreover, pegylated type I interferons treatment to HBV patients for viral reduction also reduces the miRNA. Additionally, we have also shown the immuno-pathological effects of miR-30e in systemic lupus erythematous (SLE) patients and SLE mouse model. Mechanistically, the miR-30e targets multiple negative regulators namely TRIM38, TANK, ATG5, ATG12, BECN1, SOCS1, SOCS3 of innate immune signaling pathways and enhances innate immune responses. Furthermore, sequestering of endogenous miR-30e in PBMCs of SLE patients and SLE mouse model respectively by the introduction of antagomir and locked nucleic acid based inhibitor significantly reduces type I interferon and pro-inflammatory cytokines. Collectively, our study demonstrates the novel role of miR-30e in innate immunity and its prognostic and therapeutic potential in infectious and autoimmune diseases.

Early Clearance of Mycobacterium tuberculosis Is Associated With Increased Innate Immune Responses

2019 ◽  
Author(s):  
Ayesha J Verrall ◽  
Marion Schneider ◽  
Bachti Alisjahbana ◽  
Lika Apriani ◽  
Arjan van Laarhoven ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Mycobacterium Tuberculosis ◽  
Immune Responses ◽  
Cellular Response ◽  
Ex Vivo ◽  
Interferon Γ ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Cytokine Responses ◽  
Protection Against Infection

AbstractBackgroundA proportion of tuberculosis (TB) case contacts do not become infected, even when heavily exposed. We studied the innate immune responses of TB case contacts to understand their role in protection against infection with Mycobacterium tuberculosis, termed “early clearance.”MethodsIndonesian household contacts of TB cases were tested for interferon-γ release assay (IGRA) conversion between baseline and 14 weeks post recruitment. Blood cell populations and ex vivo innate whole blood cytokine responses were measured at baseline and, in a subgroup, flow cytometry was performed at weeks 2 and 14. Immunological characteristics were measured for early clearers, defined as a persistently negative IGRA at 3 months, and converters, whose IGRA converted from negative to positive.ResultsAmong 1347 case contacts, 317 were early clearers and 116 were converters. Flow cytometry showed a resolving innate cellular response from 2 to 14 weeks in persistently IGRA-negative contacts but not converters. There were no differences in cytokine responses to mycobacterial stimuli, but compared to converters, persistently IGRA-negative contacts produced more proinflammatory cytokines following heterologous stimulation with Escherichia coli and Streptococcus pneumoniae.ConclusionsEarly clearance of M. tuberculosis is associated with enhanced heterologous innate immune responses similar to those activated during induction of trained immunity.

Tropism, replication competence, and innate immune responses of influenza virus: an analysis of human airway organoids and ex-vivo bronchus cultures

2018 ◽  
Vol 6 (11) ◽  
pp. 846-854 ◽  
Author(s):  
Kenrie P Y Hui ◽  
Rachel H H Ching ◽  
Stan K H Chan ◽  
John M Nicholls ◽  
Norman Sachs ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Ex Vivo ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Human Airway

scholarly journals The pd-l1/pd-1 axis blocks neutrophil cytotoxicity in cancer

2020 ◽  
Author(s):  
Maya Gershkovitz ◽  
Olga Yajuk ◽  
Tanya Fainsod-Levi ◽  
Zvi Granot
Keyword(s):  
Immune Responses ◽  
Tumor Growth ◽  
Tumor Cell ◽  
Therapeutic Potential ◽  
Cytotoxic T Cells ◽  
Adaptive Immune System ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Tumor Cell Apoptosis ◽  
Promote Tumor Growth

ABSTRACTThe PD-L1/PD-1 axis was shown to promote tumor growth and progression via the inhibition of anti-tumor immunity. Blocking this axis was shown to be beneficial in maintaining the anti-tumor functions of the adaptive immune system. Still, the consequences of blocking the PD-L1/PD-1 axis on innate immune responses remain largely unexplored. In this context, neutrophils were shown to consist of different subpopulations, which possess either pro- and anti-tumor properties. PD-L1-expressing neutrophils are considered pro-tumor as they can suppress cytotoxic T-cells. That said, we found that PD-L1 expression is not limited to tumor promoting neutrophils but is also evident in anti-tumor neutrophils. We show that neutrophil cytotoxicity is effectively and efficiently blocked by tumor cell expressed PD-1. Furthermore blocking of either neutrophil PD-L1 or tumor cell PD-1 maintains neutrophil cytotoxicity resulting in enhanced tumor cell apoptosis. Importantly, we show that tumor cell PD-1 blocks neutrophil cytotoxicity and promotes tumor growth via a mechanism independent of adaptive immunity. Taken together, these findings highlight the therapeutic potential of enhancing anti-tumor innate immune responses via blocking of the PD-L1/PD-1 axis.

scholarly journals Innate immune responses after stimulation with Toll-like receptor agonists in ex vivo microglial cultures and an in vivo model using mice with reduced microglia

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
James A. Carroll ◽  
Brent Race ◽  
Katie Williams ◽  
James F. Striebel ◽  
Bruce Chesebro
Keyword(s):  
Gene Expression ◽  
Immune Responses ◽  
Ex Vivo ◽  
Innate Immune ◽  
Cpg Odn ◽  
Innate Immune Responses ◽  
Tlr Signaling ◽  
Tlr Agonists ◽  
Tlr7 Agonist

Abstract Background Past experiments studying innate immunity in the central nervous system (CNS) utilized microglia obtained from neonatal mouse brain, which differ developmentally from adult microglia. These differences might impact our current understanding of the role of microglia in CNS development, function, and disease. Methods Cytokine protein secretion was compared in ex vivo P3 and adult microglial cultures after exposure to agonists for three different toll-like receptors (TLR4, lipopolysaccharide [LPS]; TLR7, imiquimod [IMQ]; and TLR9, CpG Oligodeoxynucleotide [CpG-ODN] 1585). In addition, changes in inflammatory gene expression in ex vivo adult microglia in response to the TLR agonists was assessed. Furthermore, in vivo experiments evaluated changes in gene expression associated with inflammation and TLR signaling in brains of mice with or without treatment with PLX5622 to reduce microglia. Results Ex vivo adult and P3 microglia increased cytokine secretion when exposed to TLR4 agonist LPS and to TLR7 agonist IMQ. However, adult microglia decreased expression of numerous genes after exposure to TLR 9 agonist CpG-ODN 1585. In contrast, in vivo studies indicated a core group of inflammatory and TLR signaling genes increased when each of the TLR agonists was introduced into the CNS. Reducing microglia in the brain led to decreased expression of various inflammatory and TLR signaling genes. Mice with reduced microglia showed extreme impairment in upregulation of genes after exposure to TLR7 agonist IMQ. Conclusions Cultured adult microglia were more reactive than P3 microglia to LPS or IMQ exposure. In vivo results indicated microglial influences on neuroinflammation were agonist specific, with responses to TLR7 agonist IMQ more dysregulated in mice with reduced microglia. Thus, TLR7-mediated innate immune responses in the CNS appeared more dependent on the presence of microglia. Furthermore, partial responses to TLR4 and TLR9 agonists in mice with reduced microglia suggested other cell types in the CNS can compensate for their absence.

scholarly journals Type I Alveolar Epithelial Cells Mount Innate Immune Responses during Pneumococcal Pneumonia

2012 ◽  
Vol 189 (5) ◽  
pp. 2450-2459 ◽  
Author(s):  
Kazuko Yamamoto ◽  
Joseph D. Ferrari ◽  
Yuxia Cao ◽  
Maria I. Ramirez ◽  
Matthew R. Jones ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Immune Responses ◽  
Pneumococcal Pneumonia ◽  
Innate Immune ◽  
Alveolar Epithelial Cells ◽  
Type I ◽  
Innate Immune Responses ◽  
Alveolar Epithelial
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