Corrigendum: Inulin-Type Fructans Modulates Pancreatic-Gut Innate Immune Responses and Gut Barrier Integrity during Experimental Acute Pancreatitis in a Chain Length-Dependent Manner

ABSTRACTExtracellular ATP (eATP), released as a “danger signal” by injured or stressed cells, plays an important role in the regulation of immune responses, but the relationship between ATP release and innate immune responses is still uncertain. In this study, we demonstrated that ATP was released through Toll-like receptor (TLR)-associated signaling in bothEscherichia coli-infected mice and lipopolysaccharide (LPS)- or Pam3CSK4-treated macrophages. This ATP release could be blocked completely only byN-ethylmaleimide (NEM), not by carbenoxolone (CBX), flufenamic acid (FFA), or probenecid, suggesting the key role of exocytosis in this process. Furthermore, LPS-induced ATP release could also be reduced dramatically through suppressing calcium mobilization by use of U73122, caffeine, and thapsigargin (TG). In addition, the secretion of interleukin-1β (IL-1β) and CCL-2 was enhanced significantly by ATP, in a time- and dose-dependent manner. Meanwhile, macrophage-mediated phagocytosis of bacteria was also promoted significantly by ATP stimulation. Furthermore, extracellular ATP reduced the number of invading bacteria and protected mice from peritonitis by activating purinergic receptors. Mechanistically, phosphorylation of AKT and ERK was overtly increased by ATP in antibacterial immune responses. Accordingly, if we blocked the P2X- and P2Y-associated signaling pathway by using suramin and pyridoxal phosphate-6-azo(benzene-2,4-disulfonic acid), tetrasodium salt (PPADS), the ATP-enhanced immune response was restrained significantly. Taken together, our findings reveal an internal relationship between danger signals and TLR signaling in innate immune responses, which suggests a potential therapeutic significance of calcium mobilization-mediated ATP release in infectious diseases.

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Caspase-8 is activated by cathepsin D initiating neutrophil apoptosis during the resolution of inflammation

Journal of Experimental Medicine ◽

10.1084/jem.20072152 ◽

2008 ◽

Vol 205 (3) ◽

pp. 685-698 ◽

Cited By ~ 159

Author(s):

Sébastien Conus ◽

Remo Perozzo ◽

Thomas Reinheckel ◽

Christoph Peters ◽

Leonardo Scapozza ◽

...

Keyword(s):

Immune Responses ◽

Cathepsin D ◽

Defense Mechanisms ◽

Inflammatory Responses ◽

Innate Immune ◽

Caspase 8 ◽

Neutrophil Apoptosis ◽

Dependent Manner ◽

Innate Immune Responses ◽

Inflammatory Conditions

In the resolution of inflammatory responses, neutrophils rapidly undergo apoptosis. We describe a new proapoptotic pathway in which cathepsin D directly activates caspase-8. Cathepsin D is released from azurophilic granules in neutrophils in a caspase-independent but reactive oxygen species–dependent manner. Under inflammatory conditions, the translocation of cathepsin D in the cytosol is blocked. Pharmacological or genetic inhibition of cathepsin D resulted in delayed caspase activation and reduced neutrophil apoptosis. Cathepsin D deficiency or lack of its translocation in the cytosol prolongs innate immune responses in experimental bacterial infection and in septic shock. Thus, we identified a new function of azurophilic granules that is in addition to their role in bacterial defense mechanisms: to regulate the life span of neutrophils and, therefore, the duration of innate immune responses through the release of cathepsin D.

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Decoding the role of CBLB for innate immune responses regulating systemic dissemination during Non-Tuberculous Mycobacteria infection

10.1101/2020.05.28.117663 ◽

2020 ◽

Author(s):

Srinivasu Mudalagiriyappa ◽

Jaishree Sharma ◽

Hazem F. M. Abdelaal ◽

Thomas C. Kelly ◽

Woosuk Choi ◽

...

Keyword(s):

T Cell ◽

Immune Responses ◽

Granulomatous Inflammation ◽

Innate Immune ◽

Dependent Manner ◽

Innate Immune Responses ◽

Inflammatory Monocytes ◽

Cell Immunity

AbstractNon-Tuberculous Mycobacteria (NTM) are ubiquitous in nature, present in soil and water, and cause primary leading to disseminated infections in immunocompromised individuals. NTM infections are surging in recent years due to an increase in an immune-suppressed population, medical interventions, and patients with underlying lung diseases. Host regulators of innate immune responses, frontiers for controlling infections and dissemination, are poorly defined during NTM infections. Here, we describe the role of CBLB, an E3-ubiquitin ligase, for innate immune responses and disease progression in a mouse model of NTM infection under compromised T-cell immunity. We found that CBLB thwarted NTM growth and dissemination in a time- and infection route- dependent manner. Mechanistically, we uncovered defects in many innate immune cells in the absence of Cblb, including poor responses of NK cells, inflammatory monocytes, and conventional dendritic cells. Strikingly, Cblb-deficient macrophages were competent to control NTM growth in vitro. Histopathology suggested the lack of early formation of granulomatous inflammation in the absence of CBLB. Collectively, CBLB is essential to mount productive innate immune responses and help prevent the dissemination during an NTM infection under T-cell deficiency.

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Innate Immune Responses to Adenoviral Vector-Mediated Acute Pancreatitis

Pancreas ◽

10.1097/01.mpa.0000151578.99413.88 ◽

2005 ◽

Vol 30 (2) ◽

pp. 122-129 ◽

Cited By ~ 15

Author(s):

Alexander L Shifrin ◽

Narendra Chirmule ◽

Guang-Ping Gao ◽

James M Wilson ◽

Steven E Raper

Keyword(s):

Acute Pancreatitis ◽

Immune Responses ◽

Adenoviral Vector ◽

Innate Immune ◽

Innate Immune Responses

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Multidirectional interactions are bridging human NK cells with plasmacytoid and monocyte-derived dendritic cells during innate immune responses

Blood ◽

10.1182/blood-2006-02-004028 ◽

2006 ◽

Vol 108 (12) ◽

pp. 3851-3858 ◽

Cited By ~ 53

Author(s):

Mariella Della Chiesa ◽

Chiara Romagnani ◽

Andreas Thiel ◽

Lorenzo Moretta ◽

Alessandro Moretta

Keyword(s):

Dendritic Cells ◽

Immune Responses ◽

Nk Cells ◽

De Novo ◽

Nk Cell ◽

Innate Immune ◽

Dependent Manner ◽

B Cell Differentiation ◽

Innate Immune Responses ◽

Intrinsic Resistance

AbstractDuring innate immune responses, natural killer (NK) cells may interact with both plasmacytoid dendritic cells (pDCs) and monocyte-derived dendritic cells (MDDCs). We show that freshly isolated NK cells promote the release by pDCs of IFN-α, in a CpG-dependent manner, whereas they induce IL-6 production in a CpG-independent manner. In turn pDC-derived IFN-α up-regulates NK-mediated killing, whereas IL-6 could promote B-cell differentiation. We also show that exposure to exogenous IL-12 or coculture with maturing MDDCs up-regulates the NK-cell–dependent IFN-α production by pDCs. On the other hand, NK cells cocultured with pDCs acquire the ability to kill immature MDDCs, thus favoring their editing process. Finally, we show that activated NK cells are unable to lyse pDCs because these cells display an intrinsic resistance to lysis. The exposure of pDCs to IL-3 increased their susceptibility to NK-cell cytotoxicity resulting from a de novo expression of ligands for activating NK-cell receptors, such as the DNAM-1 ligand nectin-2. Thus, different cell-to-cell interactions and various cytokines appear to control a multidirectional network between NK cells, MDDCs, and pDCs that is likely to play an important role during the early phase of innate immune responses to viral infections and to tumors.

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GNAQ Negatively Regulates Antiviral Innate Immune Responses in a Calcineurin-Dependent Manner

The Journal of Immunology ◽

10.4049/jimmunol.1900427 ◽

2019 ◽

Vol 203 (5) ◽

pp. 1288-1297

Author(s):

Ning Wang ◽

Hongjun Huang ◽

Qingqing Xiong ◽

Naiyang Chen ◽

Nanxi Xi ◽

...

Keyword(s):

Immune Responses ◽

Innate Immune ◽

Dependent Manner ◽

Innate Immune Responses

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Cocaine-induced release of CXCL10 from pericytes regulates monocyte transmigration into the CNS

The Journal of Cell Biology ◽

10.1083/jcb.201712011 ◽

2019 ◽

Vol 218 (2) ◽

pp. 700-721 ◽

Cited By ~ 9

Author(s):

Fang Niu ◽

Ke Liao ◽

Guoku Hu ◽

Susmita Sil ◽

Shannon Callen ◽

...

Keyword(s):

Immune Responses ◽

Innate Immune ◽

Innate Immune Responses ◽

Active Components ◽

Barrier Integrity ◽

Enhanced Secretion ◽

First Time ◽

The Brain

Cocaine is known to facilitate the transmigration of inflammatory leukocytes into the brain, an important mechanism underlying neuroinflammation. Pericytes are well-recognized as important constituents of the blood–brain barrier (BBB), playing a key role in maintaining barrier integrity. In the present study, we demonstrate for the first time that exposure of human brain vascular pericytes to cocaine results in enhanced secretion of CXCL10, leading, in turn, to increased monocyte transmigration across the BBB both in vitro and in vivo. This process involved translocation of σ-1 receptor (σ-1R) and interaction of σ-1R with c-Src kinase, leading to activation of the Src–PDGFR-β–NF-κB pathway. These findings imply a novel role for pericytes as a source of CXCL10 in the pericyte–monocyte cross talk in cocaine-mediated neuroinflammation, underpinning their role as active components of the innate immune responses.

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Autophagy in Macrophages: Impacting Inflammation and Bacterial Infection

Scientifica ◽

10.1155/2014/825463 ◽

2014 ◽

Vol 2014 ◽

pp. 1-13 ◽

Cited By ~ 29

Author(s):

Ali Vural ◽

John H. Kehrl

Keyword(s):

Immune Responses ◽

Host Defense ◽

Molecular Mechanisms ◽

Innate Immune ◽

Transcriptional Networks ◽

Dependent Manner ◽

Innate Immune Responses ◽

Rapid Induction ◽

Downstream Effectors ◽

Molecular Patterns

Macrophages are on the front line of host defense. They possess an array of germline-encoded pattern recognition receptors/sensors (PRRs) that recognize pathogen-associated molecular patterns (PAMPs) and which activate downstream effectors/pathways to help mediate innate immune responses and host defense. Innate immune responses include the rapid induction of transcriptional networks that trigger the production of cytokines, chemokines, and cytotoxic molecules; the mobilization of cells including neutrophils and other leukocytes; the engulfment of pathogens by phagocytosis and their delivery to lysosome for degradation; and the induction of autophagy. Autophagy is a catabolic process that normally maintains cellular homeostasis in a lysosome-dependent manner, but it also functions as a cytoprotective response that intersects with a variety of general stress-response pathways. This review focuses on the intimately linked molecular mechanisms that help govern the autophagic pathway and macrophage innate immune responses.

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