Ly6G+ Neutrophils Are Dispensable for Defense against Systemic <i>Listeria monocytogenes</i> Infection

Shi, Chao; Hohl, Tobias M.; Leiner, Ingrid; Equinda, Michele; Fan, Xiaozhou; Pamer, Eric G.

doi:10.4049/jimmunol.1101721

Cited by 115 publications

(118 citation statements)

References 41 publications

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“…Interestingly, sgp130Fc treatment caused a reduction of neutrophil accumulation in the spleen. Recent studies from Shi et al (46) and Carr et al (47) analyzed the role of neutrophils for the control of L. monocytogenes. In those studies, depletion of neutrophils had either no consequences (46) or only affected control of infection when relatively high doses of bacteria where applied (47).…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies from Shi et al (46) and Carr et al (47) analyzed the role of neutrophils for the control of L. monocytogenes. In those studies, depletion of neutrophils had either no consequences (46) or only affected control of infection when relatively high doses of bacteria where applied (47). Under the latter conditions, depletion of neutrophils mainly impaired control of infection in the liver (47).…”

Section: Discussionmentioning

confidence: 99%

“…As shown before (46,47), infection of mice with L. monocytogenes caused a rapid accumulation of neutrophils and inflammatory monocytes in spleen and liver (Supplemental Figs. 3, 4).…”

Section: Il-6 and Il-6ra Expression During Early L Monocytogenes Infmentioning

confidence: 99%

See 2 more Smart Citations

IL-6 Controls the Innate Immune Response against Listeria monocytogenes via Classical IL-6 Signaling

Hoge

Yan

Jänner

et al. 2013

The Journal of Immunology

130

107

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The cytokine IL-6 plays a protective role in immune responses against bacterial infections. However, the mechanisms of IL-6–mediated protection are only partially understood. IL-6 can signal via the IL-6R complex composed of membrane-bound IL-6Rα (mIL-6Rα) and gp130. Owing to the restricted expression of mIL-6Rα, classical IL-6 signaling occurs only in a limited number of cells such as hepatocytes and certain leukocyte subsets. IL-6 also interacts with soluble IL-6Rα proteins and these IL-6/soluble IL-6Rα complexes can subsequently bind to membrane-bound gp130 proteins and induce signaling. Because gp130 is ubiquitously expressed, this IL-6 trans-signaling substantially increases the spectrum of cells responding to IL-6. In this study, we analyze the role of classical IL-6 signaling and IL-6 trans-signaling in the innate immune response of mice against Listeria monocytogenes infection. We demonstrate that L. monocytogenes infection causes profound systemic IL-6 production and rapid loss of IL-6Rα surface expression on neutrophils, inflammatory monocytes, and different lymphocyte subsets. IL-6–deficient mice or mice treated with neutralizing anti–IL-6 mAb displayed impaired control of L. monocytogenes infection accompanied by alterations in the expression of inflammatory cytokines and chemokines, as well as in the recruitment of inflammatory cells. In contrast, restricted blockade of IL-6 trans-signaling by application or transgenic expression of a soluble gp130 protein did not restrain the control of infection. In summary, our results demonstrate that IL-6Rα surface expression is highly dynamic during the innate response against L. monocytogenes and that the protective IL-6 function is dependent on classical IL-6 signaling via mIL-6Rα.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

IL-6 Controls the Innate Immune Response against Listeria monocytogenes via Classical IL-6 Signaling

Hoge

Yan

Jänner

et al. 2013

The Journal of Immunology

130

107

View full text Add to dashboard Cite

show abstract

“…Although neutrophils are the immediate responders to any infection and injury (within few hours), monocytes are the key players in modulating the inflammation by producing cytokines, such as IL-1β, IL-6, TNF-α, as well as iNOS, and thus controlling the early phase of different infections [5,9,10,22,23] or injury [24]. Recent studies using CCR2 (-/-) mice or highly specific depletion strategies confirmed that monocytes, but not neutrophils, are important mediators in the control infections [9,22]. Furthermore, during certain microbial infection the Gr-1 hi CCR2 + monocytes can differentiate into TipDCs and produce TNF-α, iNOS [11,17,25,26] and favor the clearance of the ongoing infection (Fig.…”

Section: Infection and Injurymentioning

confidence: 99%

Monocytes in health and disease — Minireview

Karlmark

Tacke²,

Dunay³

2012

European Journal of Microbiology and Immunology

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“…inoculated with L. monocytogenes. Shi et al (69) argued that neutrophils are dispensable for the control of L. monocytogenes infection, whereas Carr et al (16) and Edelson et al (70) showed that neutrophils are protective. Discrepancies between those studies likely result from distinct experimental approaches (61).…”

Section: Discussionmentioning

confidence: 99%

The Pore-Forming Toxin Listeriolysin O Is Degraded by Neutrophil Metalloproteinase-8 and Fails To Mediate Listeria monocytogenes Intracellular Survival in Neutrophils

Arnett

Vadia

Nackerman

et al. 2014

The Journal of Immunology

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The pore-forming toxin listeriolysin O (LLO) is a major virulence factor secreted by the facultative intracellular pathogen Listeria monocytogenes. This toxin facilitates L. monocytogenes intracellular survival in macrophages and diverse nonphagocytic cells by disrupting the internalization vesicle, releasing the bacterium into its replicative niche, the cytosol. Neutrophils are innate immune cells that play an important role in the control of infections, yet it was unknown if LLO could confer a survival advantage to L. monocytogenes in neutrophils. We report that LLO can enhance the phagocytic efficiency of human neutrophils and is unable to protect L. monocytogenes from intracellular killing. To explain the absence of L. monocytogenes survival in neutrophils, we hypothesized that neutrophil degranulation leads to the release of LLO-neutralizing molecules in the forming phagosome. In support of this, L. monocytogenes is a potent inducer of neutrophil degranulation, since its virulence factors, such as LLO, facilitate granule exocytosis. Within the first few minutes of interaction with L. monocytogenes, granules can fuse with the plasma membrane at the bacterial interaction site before closure of the phagosome. Furthermore, granule products directly degrade LLO, irreversibly inhibiting its activity. The matrix metalloproteinase-8, stored in secondary granules, was identified as an endoprotease that degrades LLO, and blocking neutrophil proteases increased L. monocytogenes intracellular survival. In conclusion, we propose that LLO degradation by matrix metalloproteinase-8 during phagocytosis protects neutrophil membranes from perforation and contributes to maintaining L. monocytogenes in a bactericidal phagosome from which it cannot escape.

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Ly6G+ Neutrophils Are Dispensable for Defense against Systemic Listeria monocytogenes Infection

Cited by 115 publications

References 41 publications

IL-6 Controls the Innate Immune Response against Listeria monocytogenes via Classical IL-6 Signaling

IL-6 Controls the Innate Immune Response against Listeria monocytogenes via Classical IL-6 Signaling

Monocytes in health and disease — Minireview

The Pore-Forming Toxin Listeriolysin O Is Degraded by Neutrophil Metalloproteinase-8 and Fails To Mediate Listeria monocytogenes Intracellular Survival in Neutrophils

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