scholarly journals The Macrophage Scavenger Receptor Type A Is Expressed by Activated Macrophages and Protects the Host Against Lethal Endotoxic Shock

1997 ◽  
Vol 186 (9) ◽  
pp. 1431-1439 ◽  
Author(s):  
Richard Haworth ◽  
Nick Platt ◽  
Satish Keshav ◽  
Derralynn Hughes ◽  
Elisabeth Darley ◽  
...  
Keyword(s):  
Host Defense ◽  
Bacterial Infections ◽  
Endotoxic Shock ◽  
Scavenger Receptor ◽  
Type A ◽  
Lipoteichoic Acid ◽  
Protective Role ◽  
Infection Model ◽  
Macrophage Scavenger Receptor ◽  
Tnf Α

During gram-negative bacterial infections, lipopolysaccharide (LPS) stimulates primed macrophages (Mφ) to release inflammatory mediators such as tumor necrosis factor (TNF)-α, which can cause hypotension, organ failure, and often death. Several different receptors on Mφ have been shown to bind LPS, including the type A scavenger receptor (SR-A). This receptor is able to bind a broad range of polyanionic ligands such as modified lipoproteins and lipoteichoic acid of gram-positive bacteria, which suggests that SR-A plays a role in host defense. In this study, we used mice lacking the SR-A (SRKO) to investigate the role of SR-A in acquired immunity using a viable bacillus Calmette Guérin (BCG) infection model. We show that activated Mφ express SR-A and that this molecule is functional in assays of adhesion and endocytic uptake. After BCG infection, SRKO mice are able to recruit Mφ to sites of granuloma formation where they become activated and restrict BCG replication. However, infected mice lacking the SR-A are more susceptible to endotoxic shock and produce more TNF-α and interleukin-6 in response to LPS. In addition, we show that an antibody which blocks TNF-α activity reduces LPS-induced mortality in these mice. Thus SR-A, expressed by activated Mφ, plays a protective role in host defense by scavenging LPS as well as by reducing the release by activated Mφ of proinflammatory cytokines. Modulation of SR-A may provide a novel therapeutic approach to control endotoxic shock.

scholarly journals Febrile Core Temperature Is Essential for Optimal Host Defense in Bacterial Peritonitis

2000 ◽  
Vol 68 (3) ◽  
pp. 1265-1270 ◽  
Author(s):  
Qinqqi Jiang ◽  
Alan S. Cross ◽  
Ishwar S. Singh ◽  
T. Timothy Chen ◽  
Rose M. Viscardi ◽  
...  
Keyword(s):  
Core Temperature ◽  
Host Defense ◽  
Bacterial Infections ◽  
Bacterial Load ◽  
Cytokine Expression ◽  
Microbial Pathogens ◽  
Necrosis Factor Alpha ◽  
Bacterial Peritonitis ◽  
Tnf Α ◽  
Factor Alpha

ABSTRACT Fever, a nonspecific acute-phase response, has been associated with improved survival and shortened disease duration in infections, but the mechanisms of these beneficial responses are poorly understood. We previously reported that increasing core temperature of bacterial endotoxin (LPS)-challenged mice to the normal febrile range modified expression of tumor necrosis factor alpha (TNF-α), interleukin 1β (IL-1β), and IL-6, three cytokines critical to mounting an initial defense against microbial pathogens, but survival was not improved in the warmer animals. We speculated that our inability to show a survival benefit of optimized cytokine expression in the warmer animals reflected our use of LPS, a nonreplicating agonist, rather than an infection with viable pathogens. The objective of this study was to determine if increasing murine core temperature altered cytokine expression and improved survival in an experimental bacterial peritonitis model. We showed that housing mice at 35.5°C rather than 23°C increased core temperature from 36.5 to 37.5°C to 39.2 to 39.7°C, suppressed plasma TNF-α expression for the initial 48 h, delayed gamma interferon expression, improved survival, and reduced the bacterial load in mice infected with Klebsiella pneumoniae peritonitis. We showed that the reduced bacterial load was not caused by a direct effect on bacterial proliferation and probably reflected enhanced host defense. These data suggest that the increase in core temperature that occurs during bacterial infections is essential for optimal antimicrobial host defense.

Macrophage scavenger receptor type a attenuates the development of dextran sodium sulfate-induced colitis

2001 ◽  
Vol 120 (5) ◽  
pp. A183
Author(s):  
Willem J.S. De Villiers ◽  
Ken Westherry ◽  
Yuna Kang ◽  
Eun Lee ◽  
Gary Varilek
Keyword(s):  
Sodium Sulfate ◽  
Scavenger Receptor ◽  
Type A ◽  
Dextran Sodium Sulfate ◽  
Receptor Type ◽  
Macrophage Scavenger Receptor

scholarly journals Stabilin-1 plays a protective role against Listeria monocytogenes infection through the regulation of cytokine and chemokine production and immune cell recruitment

2021 ◽  
Author(s):  
Rita Pombinho ◽  
Jorge Pinheiro ◽  
Mariana Resende ◽  
Diana Meireles ◽  
Sirpa Jalkanen ◽  
...  
Keyword(s):  
Listeria Monocytogenes ◽  
Defense Mechanisms ◽  
Bacterial Infections ◽  
Immune Cell ◽  
Scavenger Receptor ◽  
Protective Role ◽  
Host Cells ◽  
Cell Trafficking ◽  
Host Cell Membrane ◽  
Chemokine Production

ABSTRACTScavenger receptors are part of a complex surveillance system expressed by host cells to efficiently orchestrate innate immune response against bacterial infections. Stabilin-1 (STAB-1) is a scavenger receptor involved in cell trafficking, inflammation and cancer, however its role in infection remains to be elucidated. Listeria monocytogenes (Lm) is a major intracellular human food-borne pathogen causing severe infections in susceptible hosts. Using a mouse model of infection, we demonstrate here that STAB-1 controls Lm-induced cytokine and chemokine production and immune cell accumulation in Lm-infected organs. We show that STAB-1 also regulates the recruitment of myeloid cells in response to Lm infection and contributes to clear circulating bacteria. In addition, whereas STAB-1 appears to promote bacterial uptake by macrophages, infection by pathogenic Listeria induces the down regulation of STAB-1 expression and its delocalization from the host cell membrane.We propose STAB-1 as a new SR involved in the control of Lm infection through the regulation of host defense mechanisms, a process that would be targeted by bacterial virulence factors to promote infection.

scholarly journals Protection from Lethal Gram-Positive Infection by Macrophage Scavenger Receptor–Dependent Phagocytosis

2000 ◽  
Vol 191 (1) ◽  
pp. 147-156 ◽  
Author(s):  
Christian A. Thomas ◽  
Yongmei Li ◽  
Tatsuhiko Kodama ◽  
Hiroshi Suzuki ◽  
Samuel C. Silverstein ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Critical Role ◽  
Scavenger Receptor ◽  
Lipoteichoic Acid ◽  
Peritoneal Macrophages ◽  
Type I ◽  
Dependent Manner ◽  
Gram Positive ◽  
Gram Positive Bacteria

Infections with gram-positive bacteria are a major cause of morbidity and mortality in humans. Opsonin-dependent phagocytosis plays a major role in protection against and recovery from gram-positive infections. Inborn and acquired defects in opsonin generation and/or recognition by phagocytes are associated with an increased susceptibility to bacterial infections. In contrast, the physiological significance of opsonin-independent phagocytosis is unknown. Type I and II class A scavenger receptors (SR-AI/II) recognize a variety of polyanions including bacterial cell wall products such as lipopolysaccharide (LPS) and lipoteichoic acid (LTA), suggesting a role for SR-AI/II in innate immunity to bacterial infections. Here, we show that SR-AI/II–deficient mice (MSR-A−/−) are more susceptible to intraperitoneal infection with a prototypic gram-positive pathogen, Staphylococcus aureus, than MSR-A+/+ control mice. MSR-A−/− mice display an impaired ability to clear bacteria from the site of infection despite normal killing of S. aureus by neutrophils and die as a result of disseminated infection. Opsonin-independent phagocytosis of gram-positive bacteria by MSR-A−/− macrophages is significantly decreased although their phagocytic machinery is intact. Peritoneal macrophages from control mice phagocytose a variety of gram-positive bacteria in an SR-AI/II–dependent manner. Our findings demonstrate that SR-AI/II mediate opsonin-independent phagocytosis of gram-positive bacteria, and provide the first evidence that opsonin-independent phagocytosis plays a critical role in host defense against bacterial infections in vivo.

The macrophage scavenger receptor type A directs modified proteins to antigen presentation

1999 ◽  
Vol 29 (2) ◽  
pp. 512-521 ◽  
Author(s):  
Antonino Nicoletti ◽  
Giuseppina Caligiuri ◽  
Ingrid Törnberg ◽  
Tatsuhiko Kodama ◽  
Sten Stemme ◽  
...  
Keyword(s):  
Antigen Presentation ◽  
Scavenger Receptor ◽  
Type A ◽  
Receptor Type ◽  
Macrophage Scavenger Receptor ◽  
Modified Proteins

scholarly journals GMI, an Immunomodulatory Peptide from Ganoderma microsporum, Restrains Periprosthetic Joint Infections via Modulating the Functions of Myeloid-Derived Suppressor Cells and Effector T Cells

2021 ◽  
Vol 22 (13) ◽  
pp. 6854
Author(s):  
Kuo-Ti Peng ◽  
Jiun-Liang Chen ◽  
Liang-Tseng Kuo ◽  
Pei-An Yu ◽  
Wei-Hsiu Hsu ◽  
...  
Keyword(s):  
T Cells ◽  
Bacterial Infections ◽  
Cytotoxic T Cells ◽  
Suppressor Cells ◽  
Effector T Cells ◽  
Infection Model ◽  
Myeloid Derived Suppressor Cells ◽  
Beneficial Effects ◽  
Joint Infections ◽  
Tnf Α

Periprosthetic joint infections (PJIs) caused by Staphylococcus aureus infection are difficult to treat due to antibiotic resistance. It is known that the biofilms from methicillin-resistant S. aureus (MRSA) promote expansion of myeloid-derived suppressor cells (MDSCs) to suppress T-cell proliferation and benefit bacterial infections. This study finds that GMI, a fungal immunomodulatory peptide isolated from Ganoderma microsporum, suppresses MDSC expansion to promote the proliferation of cytotoxic T cells. The enhancement is likely attributed to increased expression of IL-6 and TNF-α and reduction in ROS expression. Similar beneficial effects of GMI on the suppression of MDSC expansion and IL-6 expression are also observed in the whole blood and reduces the accumulation of MDSCs in the infected bone region in a mouse PJI infection model. This study shows that GMI is potentially useful for treating S. aureus-induced PJIs.

scholarly journals β-Sitosterol Alters the Inflammatory Response in CLP Rat Model of Sepsis by Modulation of NFκB Signaling

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Sara Kasirzadeh ◽  
Mohammad Hossein Ghahremani ◽  
Neda Setayesh ◽  
Fereshteh Jeivad ◽  
Amir Shadboorestan ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Bacterial Infections ◽  
Sham Group ◽  
Cecal Ligation ◽  
Serum Levels ◽  
Protective Role ◽  
Mrna Levels ◽  
Tnf Α ◽  
Male Wistar Rats ◽  
Host Inflammatory Response

Purpose. Sepsis originates from the host inflammatory response, especially to bacterial infections, and is considered one of the main causes of death in intensive care units. Various agents have been developed to inhibit mediators of the inflammatory response; one prospective agent is β-sitosterol (βS), a phytosterol with a structure similar to cholesterol. This study is aimed at evaluating the effects of βS on the biomarkers of inflammation and liver function in cecal ligation and puncture- (CLP-) induced septic rats. Methods. Thirty male Wistar rats were divided equally into six groups as follows: sham, CLP, CLP+dexamethasone (DX, 0.2 mg/kg), CLP+βS (1 mg/kg), CLP+imipenem (IMI, 20 mg/kg), and CLP+IMI (20 mg/kg)+βS (1 mg/kg). Serum levels of IL-1β, IL-6, IL-10, AST, ALT, and liver glutathione (GSH) were assessed by ELISA. Liver expression levels of TNF-α and NF-κBi mRNAs were evaluated by RT-qPCR. Results. Serum concentrations of IL-1β, IL-6, IL-10, ALT, and AST and mRNA levels of TNF-α and NF-κBi were all significantly higher in septic rats than in normal rats ( p < 0.05 ). Liver GSH content was markedly lower in the CLP group than that in the sham group. βS-treated rats had remarkably lower levels of IL-1β, IL-6, IL-10, TNF-α, NF-κBi, AST, and ALT (51.79%, 62.63%, 41.46%, 54.35%, 94.37%, 95.30%, 34.87%, and 46.53% lower, respectively) and greater liver GSH content (35.71% greater) compared to the CLP group ( p < 0.05 ). Conclusion. βS may play a protective role in the septic process by mitigating inflammation. This effect is at least partly mediated by inhibition of the NF-κB signaling pathway. Thus, βS can be considered as a supplementary treatment in septic patients.

scholarly journals Temporal modulation of host aerobic glycolysis determines the outcome of M. marinum infection

2018 ◽  
Author(s):  
Lu Meng ◽  
Lingling Xie ◽  
Yuanqing Kan ◽  
Lixia Liu ◽  
Wenyue Dong ◽  
...  
Keyword(s):  
Protective Effect ◽  
Host Defense ◽  
Aerobic Glycolysis ◽  
Intervention Strategy ◽  
Mycobacterial Infection ◽  
Inhibitory Effect ◽  
Infection Model ◽  
Necrosis Factor Alpha ◽  
Tnf Α

Macrophages are the first-line host defense where the invading Mycobacterium tuberculosis (Mtb) encounters. It has been recently reported that host aerobic glycolysis was elevated post the infection by a couple of virulent mycobacterial species. However, whether this metabolic transition is required for host defense against intracellular pathogens and the underlying mechanisms remain to be further investigated. By analyzing carbon metabolism, we found that macrophages infected by M. marinum, a surrogate mycobacterial specie to Mtb, showed a strong elevation of glycolysis. Next, three glycolysis inhibitors were examined for their ability to inhibit mycobacterial proliferation inside RAW264.7, a murine macrophage-like cell line. Among them, a glucose analog, 2-deoxyglucose (2-DG) displayed a protective effect on assisting host to resist mycobacterial infection, which was further validated in zebrafish-infection model. The phagocytosis of M. marinum was significantly decreased in macrophages pre-treated with 2-DG at concentrations of 0.5 and 1 mM, at which no inhibitory effect was posed on M. marinum growth in vitro. Moreover, 2-DG pre-treatment exerted a significant protective effect on zebrafish larvae to limit the proliferation of M. marinum, and such effect was correlated to tumor necrosis factor alpha (TNF-α). On the contrary, the 2-DG treatment post infection did not restrain proliferation of M. marinum in WT zebrafish, and even accelerated bacterial replication in TNF-α-/- zebrafish. Together, modulation of glycolysis prior to infection boosts host immunity against M. marinum infection, indicating a potential intervention strategy to control mycobacterial infection.

Sign in / Sign up

Export Citation Format

Share Document