scholarly journals Immune evasion by Staphylococcus aureus conferred by iron-regulated surface determinant protein IsdH

Microbiology ◽  
2009 ◽  
Vol 155 (3) ◽  
pp. 667-679 ◽  
Author(s):  
Livia Visai ◽  
Naoko Yanagisawa ◽  
Elisabet Josefsson ◽  
Andrej Tarkowski ◽  
Ilaria Pezzali ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Responses ◽  
Innate Immune ◽  
Human Neutrophils ◽  
Protective Mechanism ◽  
Innate Immune Responses ◽  
Null Mutant ◽  
Wild Type ◽  
Accelerated Degradation ◽  
Associated Proteins

The ability of Staphylococcus aureus to avoid innate immune responses including neutrophil-mediated phagocytosis is crucial for the organism to cause infection. This multifactorial process involves several secreted and cell-surface-associated proteins. In this paper we report a novel mechanism of combating neutrophils that involves iron-regulated surface determinant protein H (IsdH). The IsdH protein is part of a complex that is only expressed under iron-restricted conditions in order to bind haemoglobin and extract and transport haem into the cytoplasm. A null mutant defective in expression of IsdH, and mutants expressing variants of IsdH with substitutions in residues predicted to be involved in ligand binding, were generated from S. aureus 8325-4. The IsdH-defective mutants were shown by several measures to have reduced virulence compared with the wild-type. The mutant was engulfed more rapidly by human neutrophils in the presence of serum opsonins, survived poorly in fresh whole human blood and was less virulent in a mouse model of sepsis. The protective mechanism seems to stem from an accelerated degradation of the serum opsonin C3b.

scholarly journals Toll-like Receptor 7 Contributes to Inflammation, Organ Injury, and Mortality in Murine Sepsis

2019 ◽  
Vol 131 (1) ◽  
pp. 105-118 ◽  
Author(s):  
Wenling Jian ◽  
Lili Gu ◽  
Brittney Williams ◽  
Yan Feng ◽  
Wei Chao ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Immune Responses ◽  
Knockout Mice ◽  
Cecal Ligation ◽  
Kidney Injury ◽  
Innate Immune ◽  
Organ Injury ◽  
Innate Immune Responses ◽  
Toll Like Receptor ◽  
Wild Type

Abstract Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Sepsis remains a critical illness with high mortality. The authors have recently reported that mouse plasma RNA concentrations are markedly increased during sepsis and closely associated with its severity. Toll-like receptor 7, originally identified as the sensor for single-stranded RNA virus, also mediates host extracellular RNA-induced innate immune responses in vitro and in vivo. Here, the authors hypothesize that innate immune signaling via Toll-like receptor 7 contributes to inflammatory response, organ injury, and mortality during polymicrobial sepsis. Methods Sepsis was created by (1) cecal ligation and puncture or (2) stool slurry peritoneal injection. Wild-type and Toll-like receptor 7 knockout mice, both in C57BL/6J background, were used. The following endpoints were measured: mortality, acute kidney injury biomarkers, plasma and peritoneal cytokines, blood bacterial loading, peritoneal leukocyte counts, and neutrophil phagocytic function. Results The 11-day overall mortality was 81% in wild-type mice and 48% in Toll-like receptor 7 knockout mice after cecal ligation and puncture (N = 27 per group, P = 0.0031). Compared with wild-type septic mice, Toll-like receptor 7 knockout septic mice also had lower sepsis severity, attenuated plasma cytokine storm (wild-type vs. Toll-like receptor 7 knockout, interleukin-6: 43.2 [24.5, 162.7] vs. 4.4 [3.1, 12.0] ng/ml, P = 0.003) and peritoneal inflammation, alleviated acute kidney injury (wild-type vs. Toll-like receptor 7 knockout, neutrophil gelatinase-associated lipocalin: 307 ± 184 vs.139 ± 41-fold, P = 0.0364; kidney injury molecule-1: 40 [16, 49] vs.13 [4, 223]-fold, P = 0.0704), lower bacterial loading, and enhanced leukocyte peritoneal recruitment and phagocytic activities at 24 h. Moreover, stool slurry from wild-type and Toll-like receptor 7 knockout mice resulted in similar level of sepsis severity, peritoneal cytokines, and leukocyte recruitment in wild-type animals after peritoneal injection. Conclusions Toll-like receptor 7 plays an important role in the pathogenesis of polymicrobial sepsis by mediating host innate immune responses and contributes to acute kidney injury and mortality.

scholarly journals Tissue-Specific Patterning of Host Innate Immune Responses by Staphylococcus aureus α-Toxin

2014 ◽  
Vol 6 (5) ◽  
pp. 619-631 ◽  
Author(s):  
Russell E.N. Becker ◽  
Bryan J. Berube ◽  
Georgia R. Sampedro ◽  
Andrea C. DeDent ◽  
Juliane Bubeck Wardenburg
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Responses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Tissue Specific

scholarly journals A mouse ear skin model to study the dynamics of innate immune responses against Staphylococcus aureus biofilms

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Aizat Iman Abdul Hamid ◽  
Laurence Nakusi ◽  
Mickael Givskov ◽  
Young-Tae Chang ◽  
Claire Marquès ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Responses ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Skin Model ◽  
Mouse Ear

scholarly journals Escherichia coli and Staphylococcus aureus Elicit Differential Innate Immune Responses following Intramammary Infection

2004 ◽  
Vol 11 (3) ◽  
pp. 463-472 ◽  
Author(s):  
Douglas D. Bannerman ◽  
Max J. Paape ◽  
Jai-Wei Lee ◽  
Xin Zhao ◽  
Jayne C. Hope ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Immune Responses ◽  
Clinical Mastitis ◽  
Cytokine Response ◽  
Innate Immune ◽  
Host Recognition ◽  
Innate Immune Responses ◽  
E Coli ◽  
Intramammary Infection

ABSTRACTStaphylococcus aureusandEscherichia coliare among the most prevalent species of gram-positive and gram-negative bacteria, respectively, that induce clinical mastitis. The innate immune system comprises the immediate host defense mechanisms to protect against infection and contributes to the initial detection of and proinflammatory response to infectious pathogens. The objective of the present study was to characterize the different innate immune responses to experimental intramammary infection withE. coliandS. aureusduring clinical mastitis. The cytokine response and changes in the levels of soluble CD14 (sCD14) and lipopolysaccharide-binding protein (LBP), two proteins that contribute to host recognition of bacterial cell wall products, were studied. Intramammary infection with eitherE. coliorS. aureuselicited systemic changes, including decreased milk output, a febrile response, and induction of the acute-phase synthesis of LBP. Infection with either bacterium resulted in increased levels of interleukin 1β (IL-1β), gamma interferon, IL-12, sCD14, and LBP in milk. High levels of the complement cleavage product C5a and the anti-inflammatory cytokine IL-10 were detected at several time points followingE. coliinfection, whereasS. aureusinfection elicited a slight but detectable increase in these mediators at a single time point. Increases in IL-8 and tumor necrosis factor alpha were observed only in quarters infected withE. coli. Together, these data demonstrate the variability of the host innate immune response toE. coliandS. aureusand suggest that the limited cytokine response toS. aureusmay contribute to the well-known ability of the bacterium to establish chronic intramammary infection.

scholarly journals Viral cGAMP nuclease reveals the essential role of DNA sensing in protection against acute lethal virus infection

2020 ◽  
Vol 6 (38) ◽  
pp. eabb4565
Author(s):  
Bruno Hernáez ◽  
Graciela Alonso ◽  
Iliana Georgana ◽  
Misbah El-Jesr ◽  
Rocío Martín ◽  
...  
Keyword(s):  
Virus Infection ◽  
Immune Responses ◽  
Therapeutic Strategy ◽  
Innate Immune ◽  
Protective Mechanism ◽  
Innate Immune Responses ◽  
Dna Sensing ◽  
Nuclease Domain ◽  
The Impact

Cells contain numerous immune sensors to detect virus infection. The cyclic GMP-AMP (cGAMP) synthase (cGAS) recognizes cytosolic DNA and activates innate immune responses via stimulator of interferon genes (STING), but the impact of DNA sensing pathways on host protective responses has not been fully defined. We demonstrate that cGAS/STING activation is required to resist lethal poxvirus infection. We identified viral Schlafen (vSlfn) as the main STING inhibitor, and ectromelia virus was severely attenuated in the absence of vSlfn. Both vSlfn-mediated virulence and STING inhibitory activity were mapped to the recently discovered poxin cGAMP nuclease domain. Animals were protected from subcutaneous, respiratory, and intravenous infection in the absence of vSlfn, and interferon was the main antiviral protective mechanism controlled by the DNA sensing pathway. Our findings support the idea that manipulation of DNA sensing is an efficient therapeutic strategy in diseases triggered by viral infection or tissue damage–mediated release of self-DNA.

scholarly journals The Resistance to Host Antimicrobial Peptides in Infections Caused by Daptomycin-Resistant Staphylococcus aureus

Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 96
Author(s):  
Md Saruar Bhuiyan ◽  
Jhih-Hang Jiang ◽  
Xenia Kostoulias ◽  
Ravali Theegala ◽  
Graham J. Lieschke ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Immune Responses ◽  
Antimicrobial Peptides ◽  
Innate Immune ◽  
Cross Resistance ◽  
Infection Model ◽  
Innate Immune Responses ◽  
Persistent Infections ◽  
Zebrafish Infection

Daptomycin is an important antibiotic for the treatment of infections caused by Staphylococcus aureus. The emergence of daptomycin resistance in S. aureus is associated with treatment failure and persistent infections with poor clinical outcomes. Here, we investigated host innate immune responses against clinically derived, daptomycin-resistant (DAP-R) and -susceptible S. aureus paired isolates using a zebrafish infection model. We showed that the control of DAP-R S. aureus infections was attenuated in vivo due to cross-resistance to host cationic antimicrobial peptides. These data provide mechanistic understanding into persistent infections caused by DAP-R S. aureus and provide crucial insights into the adaptive evolution of this troublesome pathogen.

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