Natural Killer Cells Promote Tissue Injury and Systemic Inflammatory Responses During Fatal Ehrlichia-Induced Toxic Shock-Like Syndrome

Stevenson, Heather L.; Estes, Mark D.; Thirumalapura, Nagaraja; Walker, David H.; Ismail, Nahed

doi:10.2353/ajpath.2010.091110

Cited by 40 publications

(47 citation statements)

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“…We recently showed that fatal ehrlichiosis that mimics toxic shock syndrome is associated with an expansion of neutrophils and inflammatory dendritic cells in the spleen during the early stages of infection (30). These changes correlated with tissue injury, expansion of cytotoxic CD8 ϩ T cells that cause immunopathology, and suppression of protective CD4 ϩ Th1 responses (8,18).…”

Section: Changes In Myeloid Cell Populations Following Lethal Ehrlichmentioning

confidence: 99%

Neutrophils Mediate Immunopathology and Negatively Regulate Protective Immune Responses during Fatal Bacterial Infection-Induced Toxic Shock

2013

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c Ehrlichia chaffeensis is an obligate intracellular bacterium that infects primarily monocytes and macrophages and causes potentially fatal human monocytic ehrlichiosis (HME) that mimics toxic-shock-like syndrome in immunocompetent hosts. Early recruitment of neutrophils to the sites of infection is critical for the control of bacterial infection and inflammatory responses. We recently observed rapid and sustained neutrophil recruitment at a primary site of infection (peritoneum) following lethal murine ehrlichial infection compared to innocuous ehrlichial infection. We examined here the contribution of neutrophils to protective immunity or immunopathology during infection with monocytic Ehrlichia. Unexpectedly, depletion of neutrophils from lethally infected mice enhanced bacterial elimination, decreased immune-mediated pathology, and prolonged survival.

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Section: Changes In Myeloid Cell Populations Following Lethal Ehrlichmentioning

confidence: 99%

Neutrophils Mediate Immunopathology and Negatively Regulate Protective Immune Responses during Fatal Bacterial Infection-Induced Toxic Shock

2013

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“…Furthermore, in this CLP model, when bacterial clearance was investigated, discordant results were obtained depending on the nature of the antibodies used for the NK cell depletion (42). Deleterious effects of NK cell activation were reported after infection with both gram-negative (for example, E. coli [185] and Ehrlichia chaffensis [186]) and grampositive bacteria (for example, Streptococcus pneumoniae [187] and Streptococcus pyogenes [188]) independent of the site of infection (systemic, peritoneal or pulmonary). Most interestingly, NK cells may also contribute to adverse evolution of the infectious diseases as shown by their association with a Helicobacter pylori-dependent state of early-stage highgrade gastric mucosa-associated lymphoid tissue lymphoma (189) and Mycobacteria-mediated colitis in susceptible hosts (190).…”

Section: Benefits Versus Disadvantages Of Nk Cell Activation During Bmentioning

confidence: 99%

Natural Killer (NK) Cells in Antibacterial Innate Immunity: Angels or Devils?

Souza-Fonseca-Guimarães

Adib‐Conquy

Cavaillon

2011

Mol Med

132

125

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Natural killer (NK) cells were first described as immune leukocytes that could kill tumor cells and soon after were reported to kill virus-infected cells. In the mid-1980s, 10 years after their discovery, NK cells were also demonstrated to contribute to the fight against bacterial infection, particularly because of crosstalk with other leukocytes. A wide variety of immune cells are now recognized to interact with NK cells through the production of cytokines such as interleukin (IL)-2, IL-12, IL-15 and IL-18, which boost NK cell activities. The recent demonstration that NK cells express pattern recognition receptors, namely Toll-like and nucleotide oligomerization domain (NOD)-like receptors, led to the understanding that these cells are not only under the control of accessory cells, but can be directly involved in the antibacterial response thanks to their capacity to recognize pathogen-associated molecular patterns. Interferon (IFN)-γ is the predominant cytokine produced by activated NK cells. IFN-γ is a key contributor to antibacterial immune defense. However, in synergy with other inflammatory cytokines, IFN-γ can also lead to deleterious effects similar to those observed during sepsis. Accordingly, as the main source of IFN-γ in the early phase of infection, NK cells display both beneficial and deleterious effects, depending on the circumstances.

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“…Recent studies have demonstrated that NK cells are involved in IL-10 production in systemic infections [32,33]. We thus examined the role of NK cells in IL-10 production upon lethal L. monocytogenes infection.…”

Section: (F-h) Wt and Ascmentioning

confidence: 99%

“…Alternatively, PR3 might induce the secretion of mature IL-18 by activating protease-activated receptor 2 [47]. In a series of studies, IL-18R and NK cells have been shown to play a pathologic role in lethal systemic infection with Ixodes ovatus ehrlichia, a Gram-negative obligate intracellular bacterium [33,48]. The studies have shown that either IL-18R deficiency or depletion of NK cells leads to higher resistance to this pathogen, reduced liver injury, and lower IL-10 production as compared to controls.…”

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The adaptor ASC exacerbates lethal Listeria monocytogenes infection by mediating IL‐18 production in an inflammasome‐dependent and ‐independent manner

et al. 2014

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Listeria monocytogenes induces the formation of inflammasomes and subsequent caspase-1 activation, and the adaptor apoptosis-associated speck-like protein containing a CARD (ASC) is crucial for this response. However, the role of ASC in L. monocytogenes infection in vivo is unclear. In this study, we demonstrate that ASC has a detrimental effect on host defense against L. monocytogenes infection at a lethal dose (10 6 CFU), but not at a sublethal dose (10 3 CFU). During lethal L. monocytogenes infection, serum levels of IL-18 and IL-10 were markedly elevated in WT mice, but not in ASC KO mice. IL-18 KO mice were more resistant to lethal L. monocytogenes infection than WT mice and had lower levels of serum IL-10. Furthermore, blockade of IL-10 receptor resulted in a reduction in bacterial counts, suggesting that ASC and IL-18 might exacerbate L. monocytogenes infection through induction of IL-10. We noticed that maturation of IL-18 during lethal infection was partially independent of caspase-1, but was critically dependent on ASC. ASC was required for the elevation of serum neutrophil serine protease activity, which correlated with caspase-1-independent IL-18 maturation and IL-10 production. Collectively, these results suggest that ASC plays a detrimental role in lethal L. monocytogenes infection through IL-18 production in an inflammasome-dependent and -independent manner.Keywords: ASC r Caspase-1 r IL-18 r Inflammasome r Listeria monocytogenes Additional supporting information may be found in the online version of this article at the publisher's web-site IntroductionListeria monocytogenes is a Gram-positive, intracellular parasitic bacterium, which causes foodborne listeriosis in humans Correspondence: Dr. Kohsuke Tsuchiya e-mail: tsuchiya.kohsuke.5w@kyoto-u.ac.jp [1,2]. Listeria monocytogenes invades and multiplies within the cytoplasm of various types of cells, including macrophages, epithelial cells, and hepatocytes [3,4]. Several virulence factors have been reported to support the intracellular parasitism of L. monocytogenes at various steps, including invasion of host cells, escape from endosomal compartments, evasion of autophagy, utilization of cytosolic nutrient sources, and cell-to-cell spread [3,4].C 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim www.eji-journal.eu Eur. J. Immunol. 2014. 44: 3696-3707 Innate immunity 3697Listeriolysin O, a 56 kDa protein encoded by the hly gene, is a member of the cholesterol-dependent cytolysin family and plays an essential role in the escape of L. monocytogenes from phagosomes, because mutant strains lacking the hly gene are avirulent and incapable of escaping from phagosomes and of multiplying in host phagocytes [3][4][5][6]. Inflammasomes are multiprotein complexes formed typically in the cytoplasm and serve as platforms for caspase-1 activation [7]. Each inflammasome consists of pro-caspase-1 and a receptor protein that belongs to the nucleotide-binding oligomerization domain like receptor (NLR) family or the HIN-200 family. Among NLR family, CARD domain cont...

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Natural Killer Cells Promote Tissue Injury and Systemic Inflammatory Responses During Fatal Ehrlichia-Induced Toxic Shock-Like Syndrome

Abstract: Human monocytotropic ehrlichiosis is caused by

Cited by 40 publications

References 50 publications

Neutrophils Mediate Immunopathology and Negatively Regulate Protective Immune Responses during Fatal Bacterial Infection-Induced Toxic Shock

Neutrophils Mediate Immunopathology and Negatively Regulate Protective Immune Responses during Fatal Bacterial Infection-Induced Toxic Shock

Natural Killer (NK) Cells in Antibacterial Innate Immunity: Angels or Devils?

The adaptor ASC exacerbates lethal Listeria monocytogenes infection by mediating IL‐18 production in an inflammasome‐dependent and ‐independent manner

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