α-Galactosylceramide Promotes Killing of Listeria monocytogenes within the Macrophage Phagosome through Invariant NKT-Cell Activation

ABSTRACT α-Galactosylceramide (α-GalCer) has been exploited for the treatment of microbial infections. Although amelioration of infection by α-GalCer involves invariant natural killer T (iNKT)-cell activation, it remains to be determined whether macrophages (Mφ) participate in the control of microbial pathogens. In the present study, we examined the participation of Mφ in immune intervention in infection by α-GalCer using a murine model of listeriosis. Phagocytic and bactericidal activities of peritoneal Mφ from C57BL/6 mice, but not iNKT cell-deficient mice, were enhanced after intraperitoneal injection of α-GalCer despite the absence of iNKT cells in the peritoneal cavity. High levels of gamma interferon (IFN-γ) and nitric oxide (NO) were detected in the peritoneal cavities of mice treated with α-GalCer and in culture supernatants of peritoneal Mφ from mice treated with α-GalCer, respectively. Although enhanced bactericidal activity of peritoneal Mφ by α-GalCer was abrogated by endogenous IFN-γ neutralization, this was only marginally affected by NO inhibition. Similar results were obtained by using a listeriolysin O-deficient strain of Listeria monocytogenes. Moreover, respiratory burst in Mφ was increased after α-GalCer treatment. Our results suggest that amelioration of listeriosis by α-GalCer is, in part, caused by enhanced killing of L. monocytogenes within phagosomes of Mφ activated by IFN-γ from iNKT cells residing in an organ(s) other than the peritoneal cavity.

[1]  S. Kaufmann,et al.  Retracted: α‐GalCer ameliorates listeriosis by accelerating infiltration of Gr‐1+ cells into the liver , 2010, European journal of immunology.

[2]  A. Yoshimura,et al.  SOCS3 in T and NKT Cells Negatively Regulates Cytokine Production and Ameliorates ConA-Induced Hepatitis1 , 2009, The Journal of Immunology.

[3]  W. Langdon,et al.  Mechanisms of NKT cell anergy induction involve Cbl-b-promoted monoubiquitination of CARMA1 , 2009, Proceedings of the National Academy of Sciences.

[4]  K. Alitalo,et al.  Essential Roles for the Tec Family Kinases Tec and Btk in M-CSF Receptor Signaling Pathways That Regulate Macrophage Survival1 , 2008, The Journal of Immunology.

[5]  D. Portnoy,et al.  Listeriolysin O: a phagosome-specific lysin. , 2007, Microbes and infection.

[6]  I. Kawamura,et al.  Cytolysin-Dependent Escape of the Bacterium from the Phagosome Is Required but Not Sufficient for Induction of the Th1 Immune Response against Listeria monocytogenes Infection: Distinct Role of Listeriolysin O Determined by Cytolysin Gene Replacement , 2007, Infection and Immunity.

[7]  Albert Bendelac,et al.  The biology of NKT cells. , 2007, Annual review of immunology.

[8]  S. Kaufmann,et al.  Rapid Development of a Gamma Interferon-Secreting Glycolipid/CD1d-Specific Vα14+ NK1.1− T-Cell Subset after Bacterial Infection , 2006, Infection and Immunity.

[9]  A. Charbit,et al.  Listeriolysin O: a key protein of Listeria monocytogenes with multiple functions. , 2006, FEMS microbiology reviews.

[10]  S. Lippard,et al.  Visualization of nitric oxide in living cells by a copper-based fluorescent probe , 2006, Nature chemical biology.

[11]  R. Tweten,et al.  Molecular basis of listeriolysin O pH dependence. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[12]  I. Kawamura,et al.  Involvement of Reactive Oxygen Intermediate in the Enhanced Expression of Virulence‐Associated Genes of Listeria monocytogenes inside Activated Macrophages , 2005, Microbiology and immunology.

[13]  F. Hassan,et al.  Augmentation of lipopolysaccharide-induced nitric oxide production by α-galactosylceramide in mouse peritoneal cells , 2005, Journal of endotoxin research.

[14]  S. Erzurum,et al.  Visualizing inducible nitric-oxide synthase in living cells with a heme-binding fluorescent inhibitor. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[15]  S. Grinstein.  Faculty Opinions recommendation of Localized reactive oxygen and nitrogen intermediates inhibit escape of Listeria monocytogenes from vacuoles in activated macrophages. , 2003 .

[16]  M. Tsuji,et al.  Superior Protection against Malaria and Melanoma Metastases by a C-glycoside Analogue of the Natural Killer T Cell Ligand α-Galactosylceramide , 2003, The Journal of experimental medicine.

[17]  Jesse T. Myers,et al.  Localized Reactive Oxygen and Nitrogen Intermediates Inhibit Escape of Listeria monocytogenes from Vacuoles in Activated Macrophages 1 , 2003, The Journal of Immunology.

[18]  S. Chuai,et al.  Phospholipase C and phosphatidylinositol 3‐kinase signaling are involved in the exogenous arachidonic acid‐stimulated respiratory burst in human neutrophils , 2003, Journal of leukocyte biology.

[19]  G. Mayrhofer,et al.  Impaired Clearance of Herpes Simplex Virus Type 1 From Mice Lacking CD1d or NKT Cells Expressing the Semivariant Vα14-Jα281 TCR1 , 2003, The Journal of Immunology.

[20]  H. Goldfine,et al.  Macrophage intracellular signaling induced by Listeria monocytogenes. , 2002, Microbes and infection.

[21]  C. Gemmell,et al.  Virulence factor expression by Gram-positive cocci exposed to subinhibitory concentrations of linezolid. , 2002, The Journal of antimicrobial chemotherapy.

[22]  R. Steinman,et al.  Prolonged IFN-γ–producing NKT response induced with α-galactosylceramide–loaded DCs , 2002, Nature Immunology.

[23]  R. T. Sjin,et al.  Transcriptional regulation of myeloid differentiation primary response (MyD) genes during myeloid differentiation is mediated by nuclear factor Y. , 2002, Blood.

[24]  J. Glickman,et al.  CD1d-dependent macrophage-mediated clearance of Pseudomonas aeruginosa from lung , 2002, Nature Medicine.

[25]  Joel A. Swanson,et al.  The Listeria monocytogenes hemolysin has an acidic pH optimum to compartmentalize activity and prevent damage to infected host cells , 2002, The Journal of cell biology.

[26]  James M. Wilson,et al.  Natural Killer T Cell Ligand α-Galactosylceramide Enhances Protective Immunity Induced by Malaria Vaccines , 2002, The Journal of experimental medicine.

[27]  Michael T. Wilson,et al.  Natural Killer T Cell Activation Protects Mice Against Experimental Autoimmune Encephalomyelitis , 2001, The Journal of experimental medicine.

[28]  M. Kronenberg,et al.  Activation of natural killer T cells by α-galactosylceramide treatment prevents the onset and recurrence of autoimmune Type 1 diabetes , 2001, Nature Medicine.

[29]  W. Goebel,et al.  Listeria Pathogenesis and Molecular Virulence Determinants , 2001, Clinical Microbiology Reviews.

[30]  M. Taniguchi,et al.  Activation of Vα14+ Natural Killer T Cells by α-Galactosylceramide Results in Development of Th1 Response and Local Host Resistance in Mice Infected with Cryptococcus neoformans , 2001, Infection and Immunity.

[31]  L. Bockenstedt,et al.  Cutting Edge: CD1d Deficiency Impairs Murine Host Defense Against the Spirochete, Borrelia burgdorferi1 , 2000, The Journal of Immunology.

[32]  F. Chisari,et al.  Natural Killer T Cell Activation Inhibits Hepatitis B Virus Replication in Vivo , 2000, The Journal of experimental medicine.

[33]  M. Kronenberg,et al.  Tracking the Response of Natural Killer T Cells to a Glycolipid Antigen Using Cd1d Tetramers , 2000, The Journal of experimental medicine.

[34]  S. Kaufmann,et al.  Phenotypic characterization of CD8+NKT cells , 2000, European journal of immunology.

[35]  L. Kaer,et al.  α-Galactosylceramide-activated Vα14 natural killer T cells mediate protection against murine malaria. , 2000 .

[36]  K. Frei,et al.  Reduced antilisterial activity of TNF‐deficient bone marrow‐derived macrophages is due to impaired superoxide production , 1999, European journal of immunology.

[37]  H. Xiong,et al.  Induction of Protective T Cells againstListeria monocytogenes in Mice by Immunization with a Listeriolysin O-Negative Avirulent Strain of Bacteria and Liposome-Encapsulated Listeriolysin O , 1999, Infection and Immunity.

[38]  S. Kaufmann,et al.  Induction of IFN‐γ‐producing CD4+ natural killer T cells by Mycobacterium bovis bacillus Calmette Guérin , 1999, European journal of immunology.

[39]  H. Xiong,et al.  The Contributions of Reactive Oxygen Intermediates and Reactive Nitrogen Intermediates to Listericidal Mechanisms Differ in Macrophages Activated Pre- and Postinfection , 1998, Infection and Immunity.

[40]  Y. Tanaka,et al.  Natural killer-like nonspecific tumor cell lysis mediated by specific ligand-activated Valpha14 NKT cells. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[41]  A. Celada,et al.  Dexamethasone enhances macrophage colony stimulating factor- and granulocyte macrophage colony stimulating factor-stimulated proliferation of bone marrow-derived macrophages. , 1998, International immunology.

[42]  P. Berche,et al.  The ClpC ATPase of Listeria monocytogenes is a general stress protein required for virulence and promoting early bacterial escape from the phagosome of macrophages , 1998, Molecular microbiology.

[43]  T. Mak,et al.  Role for IL-15/IL-15 receptor beta-chain in natural killer 1.1+ T cell receptor-alpha beta+ cell development. , 1997, Journal of immunology.

[44]  Hiroshi Sato,et al.  CD1d-restricted and TCR-mediated activation of valpha14 NKT cells by glycosylceramides. , 1997, Science.

[45]  Joel A. Swanson,et al.  pH-dependent Perforation of Macrophage Phagosomes by Listeriolysin O from Listeria monocytogenes , 1997, The Journal of experimental medicine.

[46]  A. Bendelac,et al.  Defective IgE production by SJL mice is linked to the absence of CD4+, NK1.1+ T cells that promptly produce interleukin 4. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[47]  S. Kaufmann,et al.  Interleukin‐4‐producing CD4+ NK1.1+ TCRα/βintermediate liver lymphocytes are down‐regulated by Listeria monocytogenes , 1995 .

[48]  S. Kaufmann,et al.  IL-4 producing CD4+ TCRα βint liver lymphocytes: influence of thymus, β2-microglobulin and NK1.1 expression , 1995 .

[49]  M. Bevan,et al.  Specific immunity to Listeria monocytogenes in the absence of IFN gamma. , 1995, Immunity.

[50]  C. Nathan,et al.  Altered responses to bacterial infection and endotoxic shock in mice lacking inducible nitric oxide synthase , 1995, Cell.

[51]  J. Higginbotham,et al.  Assessment of the correlation between nitrite concentration and Listericidal activity in cultures of resident and elicited murine macrophages , 1994, Clinical and experimental immunology.

[52]  P. Campbell,et al.  Gentamicin kills intracellular Listeria monocytogenes , 1994, Infection and immunity.

[53]  W. Paul,et al.  CD4pos, NK1.1pos T cells promptly produce interleukin 4 in response to in vivo challenge with anti-CD3 , 1994, The Journal of experimental medicine.

[54]  G. Karupiah,et al.  Inhibition of viral replication by interferon-gamma-induced nitric oxide synthase. , 1993, Science.

[55]  Y. Vodovotz,et al.  Traces of bacterial lipopolysaccharide suppress IFN-gamma-induced nitric oxide synthase gene expression in primary mouse macrophages. , 1993, Journal of immunology.

[56]  R. Zinkernagel,et al.  Immune response in mice that lack the interferon-gamma receptor. , 1993, Science.

[57]  E. Unanue,et al.  Release of nitric oxide during the T cell-independent pathway of macrophage activation. Its role in resistance to Listeria monocytogenes. , 1993, Journal of immunology.

[58]  R. Good,et al.  NK1.1+ CD4+ CD8‐ thymocytes with specific lymphokine secretion , 1993, European journal of immunology.

[59]  Y. Shibata,et al.  Exudation of proliferative macrophages in local inflammation in the peritoneum , 1992, Journal of leukocyte biology.

[60]  P. Campbell,et al.  Listericidal and nonlistericidal mouse macrophages differ in complement receptor type 3‐mediated phagocytosis of L. monocytogenes and in preventing escape of the bacteria into the cytoplasm , 1992, Journal of leukocyte biology.

[61]  N. Rooijen,et al.  Selective Depletion of Liver and Splenic Macrophages Using Liposomes Encapsulating the Drug Dichloromethylene Diphosphonate: Effects on Antimicrobial Resistance , 1991, Journal of leukocyte biology.

[62]  W. Wiktor-Jedrzejczak,et al.  Total absence of colony-stimulating factor 1 in the macrophage-deficient osteopetrotic (op/op) mouse. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[63]  Pascale Fung,et al.  Listeriolysin O is essential for virulence of Listeria monocytogenes: direct evidence obtained by gene complementation , 1989, Infection and immunity.

[64]  C. Nathan,et al.  Nitric oxide. A macrophage product responsible for cytostasis and respiratory inhibition in tumor target cells , 1989, The Journal of experimental medicine.

[65]  D. Portnoy,et al.  Role of hemolysin for the intracellular growth of Listeria monocytogenes , 1988, The Journal of experimental medicine.

[66]  P. Berche,et al.  Purification, characterization, and toxicity of the sulfhydryl-activated hemolysin listeriolysin O from Listeria monocytogenes , 1987, Infection and immunity.

[67]  C. Tannenbaum,et al.  Differential Protein Synthesis by Murine Peritoneal Macrophages Elicited by Various Stimuli , 1987, Journal of leukocyte biology.

[68]  L. Hood,et al.  Expression of a murine polyclonal T cell receptor marker correlates with the use of specific members of the V beta 8 gene segment subfamily , 1987, The Journal of experimental medicine.

[69]  P. Sansonetti,et al.  Transposon mutagenesis as a tool to study the role of hemolysin in the virulence of Listeria monocytogenes , 1986, Infection and immunity.

[70]  D. Hoover,et al.  Macrophage activation to kill Leishmania tropica: defective intracellular killing of amastigotes by macrophages elicited with sterile inflammatory agents. , 1984, Journal of immunology.

[71]  Z. Werb,et al.  Regulation of elastase and plasminogen activator secretion in resident and inflammatory macrophages by receptors for the Fc domain of immunoglobulin G , 1984, The Journal of experimental medicine.

[72]  Z. Werb,et al.  Modulation of apoprotein E secretion in response to receptor-mediated endocytosis in resident and inflammatory macrophages , 1984, Journal of Experimental Medicine.

[73]  J. Činátl,et al.  Culture of macrophage cell lines from normal mouse bone marrow , 1982, Nature.

[74]  D. Shaw,et al.  Thioglycollate-elicited mouse peritoneal macrophages are less efficient than resident macrophages in antibody-dependent cell-mediated cytolysis. , 1982, Journal of immunology.

[75]  P. Campbell,et al.  Thioglycolate medium decreases resistance to bacterial infection in mice , 1980, Infection and immunity.

[76]  Z. Cohn.  Activation of mononuclear phagocytes: fact, fancy, and future. , 1978, Journal of immunology.

[77]  P. Edelson,et al.  5'-Nucleotidase activity of mouse peritoneal macrophages. I. Synthesis and degradation in resident and inflammatory populations , 1976, The Journal of experimental medicine.

[78]  L. Kaer,et al.  The natural killer T-cell ligand α-galactosylceramide prevents autoimmune diabetes in non-obese diabetic mice , 2001, Nature Medicine.

[79]  河野 鉄.  CD1d-restricted and TCR-mediated activation of V α14 NKT cells by glycosylceramides , 2000 .

[80]  M. Dinauer,et al.  Phenotype of mice and macrophages deficient in both phagocyte oxidase and inducible nitric oxide synthase. , 1999, Immunity.

[81]  J. W. Conlan,et al.  Immunity to Listeria monocytogenes. , 1998, Chemical immunology.

[82]  North Rj,et al.  Immunity to Listeria monocytogenes. , 1998 .