Neutrophil-mediated dissolution of infected host cells as a defense strategy against a facultative intracellular bacterium.

Conlan, J. Wayne; North, Robert J.

doi:10.1084/jem.174.3.741

Cited by 184 publications

(149 citation statements)

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“…Experimental murine listeriosis is instrumental in elucidating host defense mechanisms against intracellular bacteria. Cells of the innate immune system play a pivotal role as a first line of defense against L. monocytogenes [2][3][4][5] and among these, Gr-1 1 cells are central for the elimination of this pathogen at early stages of infection [6][7][8]. Numerous cytokines such as GM-CSF, IL-3, IL-6, IL-11, and SCF promote granulopoiesis by themselves and/or in concert with G-CSF [9,10].…”

Section: Introductionmentioning

confidence: 99%

“…We therefore determined whether amelioration of listeriosis by a-GalCer treatment was caused by accelerated infiltration of inflammatory cells into the liver. Because Gr-1 1 cells serve as a first line of defense against L. monocytogenes infection, in particular in the liver [6][7][8]66, 67], we compared numbers of Gr-1 1 cells in the liver before and after a-GalCer treatment. Because CD11b surface expression is up-regulated on Gr-1 1 cells after activation [68], CD11b expression was analyzed, as well.…”

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confidence: 99%

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Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1⁺ cells into the liver

Emoto

Yoshizawa

et al. 2010

Eur J Immunol

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a-Galactosylceramide (a-GalCer) activates invariant (i)NKT cells, which in turn stimulate immunocompetent cells. Although activation of iNKT cells appears critical for regulation of immune responses, it remains elusive whether protection against intracellular bacteria can be induced by a-GalCer. Here, we show that a-GalCer treatment ameliorates murine listeriosis, and inhibits inflammation following Listeria monocytogenes infection. Liver infiltration of Gr-1 1 cells and c/d T cells was accelerated by a-GalCer treatment. Gr-1 1 cell and c/d T-cell depletion exacerbated listeriosis in a-GalCer-treated mice, and this effect was more pronounced after depletion of Gr-1 1 cells than that of c/d T cells. Although GM-CSF and IL-17 were secreted by NKT cells after a-GalCer treatment, liver infiltration of Gr-1 1 cells was not prevented by neutralizing mAb. In parallel to the numerical increase of CD11b 1 Gr-1 1 cells in the liver following a-GalCer treatment, CD11b À Gr-1 1 cells were numerically reduced in the bone marrow. In addition, respiratory burst in Gr-1 1 cells was enhanced by a-GalCer treatment. Our results indicate that a-GalCer-induced antibacterial immunity is caused, in part, by accelerated infiltration of Gr-1 1 cells and to a lesser degree of c/d T cells into the liver. We also suggest that the infiltration of Gr-1 1 cells is caused by an accelerated supply from the bone marrow.Key words: a-galactosylceramide . L. monocytogenes . NKT cell Supporting Information available online IntroductionListeria monocytogenes is a Gram-positive facultative intracellular bacterial pathogen, which causes disseminated infection in immunocompromised hosts [1]. Experimental murine listeriosis is instrumental in elucidating host defense mechanisms against intracellular bacteria. Cells of the innate immune system play a pivotal role as a first line of defense against L. monocytogenes [2-5] and among these, Gr-1 1 cells are central for the elimination of this pathogen at early stages of infection [6][7][8]. Numerous cytokines such as GM-CSF, IL-3, IL-6, IL-11, and SCF promote granulopoiesis by themselves and/or in concert with G-CSF [9,10]. G-CSF is indispensable for both steady-state and emergency granulopoiesis [11][12][13][14], and IL-17 regulates G-CSF secretion [9,10,[15][16][17][18]. In addition to Gr-1 1 cells, g/d T cells also participate in early protection against 1328L. monocytogenes infection [19][20][21][22]. The vast majority of L. monocytogenes organisms are trapped in the liver immediately after systemic infection [23] and hence, immunocompetent cells that reside in, and/or migrate into, the liver are critical for infection control.NKT cells represent a unique subset of T lymphocytes, which are characterized by the co-expression of NK cell markers such as NKR-P1B/C (NK1.1; CD161) [24]. In the mouse, the majority of NKT cells express an invariant (i) TCR composed of Va14/Ja18 gene segments, i.e. iNKT cells [24]. In contrast to conventional T cells, which recognize peptide antigens presented by polymorphic MHC ...

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Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1⁺ cells into the liver

Emoto

Yoshizawa

et al. 2010

Eur J Immunol

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“…Its ability to invade and multiply in a wide range of mammalian cells (Vazquez-Boland et al, 2001) is essential for development of systemic listeriosis. For example, the ability of L. monocytogenes to invade nonphagocytic cells plays an important role in this organism's traversal of the intestinal barrier (Lecuit et al, 2001;MacDonald & Carter, 1980;Racz et al, 1972), and its ability to multiply in hepatocytes is essential for causing a systemic infection (Conlan & North, 1991;Gaillard et al, 1996). Several bacterial factors that mediate internalization events have been identified.…”

Section: Introductionmentioning

confidence: 99%

σ B contributes to Listeria monocytogenes invasion by controlling expression of inlA and inlB

2005

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The ability of Listeria monocytogenes to invade non-phagocytic cells is important for development of a systemic listeriosis infection. The authors previously reported that a L. monocytogenes DsigB strain is defective in invasion into human intestinal epithelial cells, in part, due to decreased expression of a major invasion gene, inlA. To characterize additional invasion mechanisms under the control of s B , mutants were generated carrying combinations of in-frame deletions in inlA, inlB and sigB. Quantitative assessment of bacterial invasion into the human enterocyte Caco-2 and hepatocyte HepG-2 cell lines demonstrated that s B contributes to both InlA and InlB-mediated invasion of L. monocytogenes. Previous identification of the s B -dependent P2 prfA promoter upstream of the major virulence gene regulator, positive regulatory factor A (PrfA), suggested that the contributions of s B to expression of various virulence genes, including inlA, could be at least partially mediated through PrfA. To test this hypothesis, relative invasion capabilities of DsigB and DprfA strains were compared. Exponential-phase cells of the DsigB and DprfA strains were similarly defective at invasion; however, stationary-phase DsigB cells were significantly less invasive than stationary-phase DprfA cells, suggesting that the contributions of s B to invasion extend beyond those mediated through PrfA in stationary-phase L. monocytogenes. TaqMan quantitative reverse-transcriptase PCRs further demonstrated that expression of inlA and inlB was greatly increased in a s B -dependent manner in stationary-phase L. monocytogenes. Together, results from this study provide strong biological evidence of a critical role for s B in L. monocytogenes invasion into non-phagocytic cells, primarily mediated through control of inlA and inlB expression.

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“…During systemic infection of mice with L. monocytogenes, the liver serves as a major site of bacterial replication (17)(18)(19)(20). Western blot analysis indicated that the mouse liver expresses Tuba (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In order to more directly test the hypothesis that the inlC.K173A mutant is compromised for spreading in the liver, we performed histological analysis. L. monocytogenes is known to produce foci in the liver that result from infection of hepatocytes (17,18,20). The size of these foci may reflect the efficiency of bacterial spreading.…”

Section: Resultsmentioning

confidence: 99%

Impact of the Listeria monocytogenes Protein InlC on Infection in Mice

et al. 2013

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The bacterial pathogen Listeria monocytogenes causes serious food-borne illnesses in pregnant women and the immunocompromised. L. monocytogenes promotes its internalization into host epithelial cells and then uses an F-actin-dependent motility process to spread from infected cells to surrounding healthy cells. In cultured enterocytes, efficient spread of L. monocytogenes requires the secreted bacterial protein InlC. InlC promotes dissemination by physically interacting with and antagonizing the function of the human adaptor protein Tuba. Here we examine the role of InlC and its interaction with host Tuba during infection in mice. The study took advantage of a single-amino-acid substitution (K173A) in InlC that impairs binding to human Tuba but does not affect InlC-mediated inhibition of the NF-B pathway. Mice were inoculated intravenously with the wild-type L. monocytogenes strain EGD, an isogenic strain deleted for the inlC gene (⌬inlC), or a strain expressing K173A mutant InlC (inlC.K173A). The 50% lethal doses (LD 50 ) for the ⌬inlC or inlC.K173A mutant strain were approximately 4-or 6-fold greater than that for the wild-type strain, indicating a role for inlC in virulence. Compared to the wild-type strain, the inlC.K173A mutant strain exhibited lower bacterial loads in the liver. Histological analysis of livers indicated that the two inlC mutant strains produced smaller foci of infection than did the wild-type strain. These smaller foci are consistent with a role for InlC in cell-tocell spread in vivo. Taken together, these results provide evidence that interaction of InlC with host Tuba is important for full virulence.L isteria monocytogenes is a food-borne, intracellular pathogen that causes gastroenteritis, abortions, or meningitis with a high mortality rate (1, 2). L. monocytogenes replicates within mammalian cells and spreads from one cell to another through a motility process that is dependent on the host F-actin cytoskeleton (3). Spreading is initiated by the bacterial surface protein ActA, which stimulates the formation of F-actin "comet tails" that propel L. monocytogenes through the cytoplasm. Motile bacteria contact the inner surface of the host cell plasma membrane and induce the formation of pathogen-containing protrusions that are engulfed by neighboring cells. Cell-to-cell spread is critical for virulence, since an L. monocytogenes strain containing a null mutation in the actA gene is severely compromised for disease in a mouse model (4). The 50% lethal dose (LD 50 ) for this actA mutant is approximately 3 logs higher than that of the isogenic wild-type (wt) strain (4).ActA is thought to be required for spreading in all cell types. In cells that do not form tight barriers, such as macrophages or fibroblasts, actin-dependent motility may be sufficient for formation of bacterial protrusions (5). In these cell types, the force provided by motility may be the sole factor controlling protrusion generation. However, many tissues infected by L. monocytogenes contain polarized cells connected by cell-...

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Neutrophil-mediated dissolution of infected host cells as a defense strategy against a facultative intracellular bacterium.

Cited by 184 publications

References 12 publications

Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1⁺ cells into the liver

Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1⁺ cells into the liver

σ B contributes to Listeria monocytogenes invasion by controlling expression of inlA and inlB

Impact of the Listeria monocytogenes Protein InlC on Infection in Mice

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Neutrophil-mediated dissolution of infected host cells as a defense strategy against a facultative intracellular bacterium.

Cited by 184 publications

References 12 publications

Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1+ cells into the liver

Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1+ cells into the liver

σ B contributes to Listeria monocytogenes invasion by controlling expression of inlA and inlB

Impact of the Listeria monocytogenes Protein InlC on Infection in Mice

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Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1⁺ cells into the liver

Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1⁺ cells into the liver