Persistence Without Pathology in Phosphoglycan-Deficient Leishmania major

Leishmania infections involve an acute phase of replication within macrophages, typically associated with pathology. After recovery parasites persist for long periods, which can lead to severe disease upon reactivation. Unlike the role of host factors, parasite factors affecting persistence are poorly understood. Leishmania major lacking phosphoglycans (lpg2-) were unable to survive in sand flies and macrophages, but retained the ability to persist indefinitely in the mammalian host without inducing disease. The L. major lpg2- thus provides a platform for probing parasite factors implicated in persistence and its role in disease and immunity.

[1]  C. Bogdan,et al.  Leishmania-host-cell interaction: complexities and alternative views. , 2000, Parasitology today.

[2]  G. H. Coombs,et al.  Leishmania mexicana cysteine proteinase-deficient mutants have attenuated virulence for mice and potentiate a Th1 response. , 1998, Journal of immunology.

[3]  C. Bogdan,et al.  Invasion, control and persistence of Leishmania parasites. , 1996, Current opinion in immunology.

[4]  L. Garraway,et al.  The role(s) of lipophosphoglycan (LPG) in the establishment of Leishmania major infections in mammalian hosts , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[5]  S. Beverley,et al.  A lipophosphoglycan-independent method for isolation of infective Leishmania metacyclic promastigotes by density gradient centrifugation. , 2001, Experimental parasitology.

[6]  S. Beverley,et al.  Golgi GDP-mannose Uptake Requires Leishmania LPG2 , 1997, The Journal of Biological Chemistry.

[7]  R. López-Vélez,et al.  Leishmania and human immunodeficiency virus coinfection: the first 10 years , 1997, Clinical microbiology reviews.

[8]  S. Beverley,et al.  The role of phosphoglycans in Leishmania-sand fly interactions. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[9]  Y. Belkaid,et al.  A Natural Model of Leishmania major Infection Reveals a Prolonged “Silent” Phase of Parasite Amplification in the Skin Before the Onset of Lesion Formation and Immunity , 2000, The Journal of Immunology.

[10]  Y. Stierhof,et al.  Proteophosphoglycans from Leishmania promastigotes and amastigotes. , 1999, Biochemical Society transactions.

[11]  P. Bretscher,et al.  Immune Elimination of Leishmania major in Mice: Implications for Immune Memory, Vaccination, and Reactivation Disease1 , 2001, The Journal of Immunology.

[12]  C. Bogdan,et al.  Reactivation of latent leishmaniasis by inhibition of inducible nitric oxide synthase , 1996, The Journal of experimental medicine.

[13]  S. Beverley,et al.  Development of a safe live Leishmania vaccine line by gene replacement. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[14]  P. Orlandi,et al.  Structure of the lipid moiety of the Leishmania donovani lipophosphoglycan. , 1987, The Journal of biological chemistry.

[15]  T. Boon,et al.  A limiting dilution assay for quantifying Leishmania major in tissues of infected mice , 1985, Parasite immunology.

[16]  C. Bogdan,et al.  Fibroblasts as Host Cells in Latent Leishmaniosis , 2000, The Journal of experimental medicine.

[17]  Y. Belkaid,et al.  CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity , 2002, Nature.

[18]  S. Beverley,et al.  Is lipophosphoglycan a virulence factor? A surprising diversity between Leishmania species. , 2001, Trends in parasitology.

[19]  A. Bacic,et al.  The structure of Leishmania major amastigote lipophosphoglycan. , 1993, The Journal of biological chemistry.

[20]  C. Bogdan,et al.  The immune response to Leishmania: mechanisms of parasite control and evasion. , 1998, International journal for parasitology.

[21]  T. Ilg,et al.  Phosphoglycan Repeat-deficient Leishmania mexicanaParasites Remain Infectious to Macrophages and Mice* , 2001, The Journal of Biological Chemistry.

[22]  S. Beverley,et al.  A specialized pathway affecting virulence glycoconjugates of Leishmania. , 1995, Science.

[23]  M. McConville,et al.  Recognition of the major cell surface glycoconjugates of Leishmania parasites by the human serum mannan-binding protein. , 1994, Molecular and biochemical parasitology.

[24]  S. Beverley,et al.  Lipophosphoglycan is a virulence factor distinct from related glycoconjugates in the protozoan parasite Leishmania major. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[25]  Y. Belkaid,et al.  The Role of Interleukin (IL)-10 in the Persistence of Leishmania major in the Skin after Healing and the Therapeutic Potential of Anti–IL-10 Receptor Antibody for Sterile Cure , 2001, The Journal of experimental medicine.

[26]  E. Handman,et al.  Persistence of virulent Leishmania major in murine cutaneous leishmaniasis: a possible hazard for the host , 1993, Infection and immunity.

[27]  G. Feng,et al.  Regulation of macrophage IL‐12 synthesis by Leishmania phosphoglycans , 1999, European journal of immunology.

[28]  R. Zinkernagel,et al.  Exacerbation of experimental murine cutaneous leishmaniasis with CD4+ Leishmania major‐specific T cell lines or clones which secrete interferon‐γ and mediate parasite‐specific delayed‐type hypersensitivity , 1991, European journal of immunology.

[29]  M. McConville,et al.  Function and assembly of the Leishmania surface coat. , 2001, International journal for parasitology.