Role of macrophages in restricting herpes simplex virus type 1 growth after ocular infection.

PURPOSE To investigate the role macrophages play in controlling herpes simplex virus (HSV)-1 replication after infection of the murine cornea. METHODS Macrophage depletion in selected tissues before or after virus infection was achieved by repeated subconjunctival (SCJ) and/or intravenous (IV) injection of liposomes containing dichloromethylene diphosphonate (L-Cl2MDP). Controls received liposomes containing phosphate-buffered saline (L-PBS). The efficiency of depletion was evaluated by histologic examination. Virus content in infected tissues was determined by standard plaque assay. Delayed-type hypersensitivity (DTH) responsiveness was assessed using the ear-swelling assay. Antibody isotype responses to virus antigens and cytokine production were monitored by enzyme-linked immunosorbent assay. RESULTS Balb/c mice given SCJ injection of L-Cl2MDP 4 and 2 days before HSV-1 corneal infection were found to have ocular virus titers as much as 10(5)-fold higher than that seen in the L-PBS-treated controls 8 days after infection. When L-Cl2MDP treatment was delayed until 2 and 4 days after infection, virus titers in the eye were analogous to those in the control animals. Subconjunctival and submandibular lymph node macrophages in mice given local (SCJ) L-Cl2MDP pretreatment were profoundly reduced, whereas the number of corneal Langerhans' cells and lymph node dendritic cells remained unchanged. Local L-Cl2MDP pretreatment was associated with significantly reduced DTH responsiveness to HSV-1 antigen, and an alteration in selected antibody isotype production. Depletion of macrophages in the subconjunctival tissue before corneal infection was not accompanied by enhanced virus growth at early times (2 or 4 days) after infection. CONCLUSIONS Macrophages play an important role in restricting HSV-1 growth after corneal infection. These cells appear to be required for the development of an acquired immune response, presumably by functioning in antigen processing and presentation. The hypothesis that macrophages are major participants in innate immunity to HSV-1 corneal infection was not supported.

[1]  H. Virgin,et al.  Interferons Regulate the Phenotype of  Wild-type and Mutant Herpes Simplex Viruses In Vivo , 1999, The Journal of experimental medicine.

[2]  R. Zinkernagel,et al.  Cutting Edge Commentary: Immune Responses in the Absence of Costimulation: Viruses Know the Trick , 1998, The Journal of Immunology.

[3]  R. Hendricks,et al.  B7 costimulatory requirements of T cells at an inflammatory site. , 1998, Journal of immunology.

[4]  M. Heemskerk,et al.  Role of spleen macrophages in innate and acquired immune responses against mouse hepatitis virus strain A59. , 1997, Immunology.

[5]  H. Staats,et al.  Intranasal immunization is superior to vaginal, gastric, or rectal immunization for the induction of systemic and mucosal anti-HIV antibody responses. , 1997, AIDS research and human retroviruses.

[6]  G. Karupiah,et al.  Different roles for CD4+ and CD8+ T lymphocytes and macrophage subsets in the control of a generalized virus infection , 1996, Journal of virology.

[7]  Y. Takei,et al.  Liposome‐encapsulated dichloromethylene diphosphonate induces macrophage apoptosis in vivo and in vitro , 1996, Journal of leukocyte biology.

[8]  H. Staats,et al.  Mucosal immunity to HIV-1: systemic and vaginal antibody responses after intranasal immunization with the HIV-1 C4/V3 peptide T1SP10 MN(A). , 1996, Journal of immunology.

[9]  T. K. van den Berg,et al.  Apoptosis of macrophages induced by liposome-mediated intracellular delivery of clodronate and propamidine. , 1996, Journal of immunological methods.

[10]  N. Van Rooijen,et al.  The role of macrophages in Acanthamoeba keratitis. , 1996, Investigative ophthalmology & visual science.

[11]  T. Tumpey,et al.  Neutrophil-mediated suppression of virus replication after herpes simplex virus type 1 infection of the murine cornea , 1996, Journal of virology.

[12]  B. Rouse,et al.  Role of macrophages and dendritic cells in primary cytotoxic T lymphocyte responses. , 1995, International immunology.

[13]  Shunxin Chen,et al.  Synergistic anti-herpes effect of TNF-α and IFN-γ in human corneal epithelial cells compared with that in corneal fibroblasts , 1994 .

[14]  N. Van Rooijen,et al.  Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications. , 1994, Journal of immunological methods.

[15]  M. Jutila,et al.  Elimination of mouse splenic macrophages correlates with increased susceptibility to experimental disseminated candidiasis. , 1994, Journal of immunology.

[16]  F. Sallusto,et al.  Efficient presentation of soluble antigen by cultured human dendritic cells is maintained by granulocyte/macrophage colony-stimulating factor plus interleukin 4 and downregulated by tumor necrosis factor alpha , 1994, The Journal of experimental medicine.

[17]  S. H. Chen,et al.  Synergistic anti-HSV effect of tumor necrosis factor alpha and interferon gamma in human corneal fibroblasts is associated with interferon beta induction. , 1993, Antiviral research.

[18]  A. Cerami,et al.  Genomic cloning and promoter analysis of macrophage inflammatory protein (MIP)-2, MIP-1 alpha, and MIP-1 beta, members of the chemokine superfamily of proinflammatory cytokines. , 1993, Journal of immunology.

[19]  Austyn Jm.  Antigen uptake and presentation by dendritic leukocytes. , 1992 .

[20]  T. Tumpey,et al.  Critical role of corneal Langerhans cells in the CD4- but not CD8-mediated immunopathology in herpes simplex virus-1-infected mouse corneas. , 1992, Journal of immunology.

[21]  H. Staats,et al.  Anti-glycoprotein D monoclonal antibody protects against herpes simplex virus type 1-induced diseases in mice functionally depleted of selected T-cell subsets or asialo GM1+ cells , 1991, Journal of virology.

[22]  T. Tumpey,et al.  Endogenously produced interferon alpha protects mice from herpes simplex virus type 1 corneal disease. , 1991, The Journal of general virology.

[23]  N. Van Rooijen,et al.  A new method for removal of mononuclear phagocytes from heterogeneous cell populations in vitro, using the liposome-mediated macrophage 'suicide' technique. , 1990, Journal of immunological methods.

[24]  R. Steinman,et al.  Migration and maturation of Langerhans cells in skin transplants and explants , 1990, The Journal of experimental medicine.

[25]  J. Oakes,et al.  Ocular avirulence of a herpes simplex virus type 1 strain is associated with heightened sensitivity to alpha/beta interferon , 1990, Journal of virology.

[26]  N. Rooijen,et al.  Repopulation of Macrophages in Popliteal Lymph Nodes of Mice After Liposome‐Mediated Depletion , 1990, Journal of leukocyte biology.

[27]  L. Smith,et al.  Quantitation of purified monoclonal antibody needed to prevent HSV-1 induced stromal keratitis in mice. , 1989, Current eye research.

[28]  S. Knight,et al.  Localization of antigen on lymph node dendritic cells after exposure to the contact sensitizer fluorescein isothiocyanate. Functional and morphological studies , 1987, The Journal of experimental medicine.

[29]  E. Unanue,et al.  The basis for the immunoregulatory role of macrophages and other accessory cells. , 1987, Science.

[30]  J. Oakes,et al.  Superiority of antibody versus delayed hypersensitivity in clearance of HSV-1 from eye. , 1987, Investigative ophthalmology & visual science.

[31]  G. Kraal,et al.  Langerhans' cells, veiled cells, and interdigitating cells in the mouse recognized by a monoclonal antibody , 1986, The Journal of experimental medicine.

[32]  S. Kayes,et al.  Resolution of HSV corneal infection in the absence of delayed-type hypersensitivity. , 1985, Investigative ophthalmology & visual science.

[33]  J. Rector,et al.  Lyt-1+ T cells participate in recovery from ocular herpes simplex virus type 1 infection. , 1984, Investigative ophthalmology & visual science.

[34]  H. Grey,et al.  Requirements for the processing of antigen by antigen-presenting B cells. II. Biochemical comparison of the fate of antigen in B cell tumors and macrophages. , 1982, Journal of immunology.

[35]  H. Grey,et al.  Requirements for the processing of antigens by antigen-presenting B cells. I. Functional comparison of B cell tumors and macrophages. , 1982, Journal of immunology.

[36]  E. Unanue,et al.  Identification of a macrophage antigen-processing event required for I-region-restricted antigen presentation to T lymphocytes. , 1981, Journal of immunology.

[37]  T. Merigan,et al.  Cellular immunity and herpesvirus infections in cardiac-transplant patients. , 1977, The New England journal of medicine.

[38]  A. Notkins,et al.  PREVENTION OF CELL-TO-CELL SPREAD OF HERPES SIMPLEX VIRUS BY LEUKOCYTES , 1973, The Journal of experimental medicine.

[39]  Tilney Nl.  Patterns of lymphatic drainage in the adult laboratory rat. , 1971 .

[40]  A. Allison,et al.  Role of macrophages and antibody in resistance of mice against yellow fever virus. , 1971, Journal of immunology.

[41]  M. Hirsch,et al.  Selective effects of anti-macrophage serum, silica and anti-lymphocyte serum on pathogenesis of herpes virus infection of young adult mice. , 1970, Journal of immunology.

[42]  Richard T. Johnson.  THE PATHOGENESIS OF HERPES VIRUS ENCEPHALITIS. II. A CELLULAR BASIS FOR THE DEVELOPMENT OF RESISTANCE WITH AGE. , 1964 .

[43]  I. Kimber,et al.  Tumour necrosis factor-alpha is required for accumulation of dendritic cells in draining lymph nodes and for optimal contact sensitization. , 1995, Immunology.

[44]  P. Morahan,et al.  Macrophages and other nonspecific defenses: role in modulating resistance against herpes simplex virus. , 1992, Current topics in microbiology and immunology.

[45]  D. Falke,et al.  In vivo protective effect of tumour necrosis factor alpha against experimental infection with herpes simplex virus type 1. , 1991, The Journal of general virology.

[46]  M. Ito,et al.  Antiviral effects of recombinant human tumor necrosis factor. , 1987, Lymphokine research.

[47]  S. Mittnacht,et al.  Antiviral effects of recombinant tumour necrosis factor in vitro , 1986, Nature.

[48]  E. Unanue,et al.  Decrease in macrophage antigen catabolism caused by ammonia and chloroquine is associated with inhibition of antigen presentation to T cells. , 1982, Proceedings of the National Academy of Sciences of the United States of America.