The p110δ isoform of phosphatidylinositol 3-kinase controls susceptibility to Leishmania major by regulating expansion and tissue homing of regulatory T cells

Journal of Immunology

Volumn 183, Issue 3, 2009, Pages 1921-1933

  Liu, Dong ^a   Zhang, Tingting ^a   Marshall, Aaron J ^a   Okkenhaug, Klaus ^b   Vanhaesebroeck, Bart ^c   Uzonna, Jude E ^a  

^a UNIVERSITY OF MANITOBA   (Canada)

^b BABRAHAM INSTITUTE   (United Kingdom)

^c QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

GAMMA INTERFERON; NITRIC OXIDE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN P110; TUMOR NECROSIS FACTOR; 1 PHOSPHATIDYLINOSITOL 3 KINASE P110 SUBUNIT, MOUSE; 1-PHOSPHATIDYLINOSITOL 3-KINASE P110 SUBUNIT, MOUSE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CELL EXPANSION; CELLULAR IMMUNITY; CONTROLLED STUDY; CYTOKINE PRODUCTION; DENDRITIC CELL; EFFECTOR CELL; FEMALE; GENETIC RESISTANCE; GENETIC SUSCEPTIBILITY; IMMUNE RESPONSE; INFECTION SENSITIVITY; LEISHMANIA MAJOR; LEISHMANIASIS; LYMPHOCYTE HOMING; LYMPHOCYTE PROLIFERATION; MACROPHAGE; MOUSE; NONHUMAN; OUTCOME ASSESSMENT; PRIORITY JOURNAL; REGULATORY T LYMPHOCYTE; WILD TYPE; ANIMAL; CELL PROLIFERATION; DISEASE PREDISPOSITION; ENZYMOLOGY; GENETICS; IMMUNITY; IMMUNOLOGY; MISSENSE MUTATION; NEUTROPHIL CHEMOTAXIS; PHYSIOLOGY; SKIN LEISHMANIASIS;

1-PHOSPHATIDYLINOSITOL 3-KINASE; ANIMALS; CELL PROLIFERATION; CHEMOTAXIS, LEUKOCYTE; DISEASE SUSCEPTIBILITY; IMMUNITY; LEISHMANIA MAJOR; LEISHMANIASIS, CUTANEOUS; MICE; MUTATION, MISSENSE; T-LYMPHOCYTES, REGULATORY;

EID: 68149100422     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.0901099     Document Type: Article

References (60)

1. Reiner, S. L., and R. M. Locksley. 1995. The regulation of immunity to Leishmania major. Annu. Rev. Immunol. 13: 151-177.
2. + subsets during murine Leishmania major infection. Res. Immunol. 142: 28-32.
3. + T-cell subsets in the regulation of parasite immunity and disease. Immunol. Rev. 112: 161-182.
4. Kane, M. M., and D. M. Mosser. 2001. The role of IL-10 in promoting disease progression in leishmaniasis. J. Immunol. 166: 1141-1147. (Pubitemid 32060273)
5. Groux, H., F. Cottrez, M. Rouleau, S. Mauze, S. Antonenko, S. Hurst, T. McNeil, M. Bigler, M. G. Roncarolo, and R. L. Coffman. 1999. A transgenic model to analyze the immunoregulatory role of IL-10 secreted by antigen-presenting cells. J. Immunol. 162: 1723-1729.
6. + regulatory T cells in Leishmania infection. Expert Opin. Biol. Ther. 3: 875-885.
7. + regulatory T cells control Leishmania major persistence and immunity. Nature 420: 502-507.
8. - Th1 cells are the source of IL-10-mediated immune suppression in chronic cutaneous leishmaniasis. J. Exp. Med. 204: 285-297.
9. Mosser, D. M., and L. A. Rosenthal. 1993. Leishmania-macrophage interactions: multiple receptors, multiple ligands and diverse cellular responses. Semin. Cell. Biol. 4: 315-322.
10. Okkenhaug, K., and B. Vanhaesebroeck. 2003. PI3K in lymphocyte development, differentiation and activation. Nat. Rev. Immunol. 3: 317-330.
11. + regulatory T cells. J. Immunol. 177: 6598-6602.
12. Okkenhaug, K., A. Bilancio, J. L. Emery, and B. Vanhaesebroeck. 2004. Phosphoinositide 3-kinase in T cell activation and survival. Biochem. Soc. Trans. 32: 332-335.
13. Vanhaesebroeck, B., K. Ali, A. Bilancio, B. Geering, and L. C. Foukas. 2005. Signalling by PI3K isoforms: insights from gene-targeted mice. Trends Biochem. Sci. 30: 194-204.
14. Vanhaesebroeck, B., M. J. Welham, K. Kotani, R. Stein, P. H. Warne, M. J. Zvelebil, K. Higashi, S. Volinia, J. Downward, and M. D. Waterfield. 1997. P110δ, a novel phosphoinositide 3-kinase in leukocytes. Proc. Natl. Acad. Sci. USA 94: 4330-4335.
15. Ruhland, A., N. Leal, and P. E. Kima. 2007. Leishmania promastigotes activate PI3K/Akt signalling to confer host cell resistance to apoptosis. Cell. Microbiol. 9: 84-96.
16. Jiang, B. H., and L. Z. Liu. 2008. PI3K/PTEN signaling in tumorigenesis and angiogenesis. Biochim. Biophys. Acta 1784: 150-158.
17. Carnero, A., C. Blanco-Aparicio, O. Renner, W. Link, and J. F. Leal. 2008. The PTEN/PI3K/AKT signalling pathway in cancer, therapeutic implications. Curr. Cancer Drug Targets 8: 187-198.
18. Kuroda, S., M. Nishio, T. Sasaki, Y. Horie, K. Kawahara, M. Sasaki, M. Natsui, T. Matozaki, H. Tezuka, T. Ohteki, et al. 2008. Effective clearance of intracellular Leishmania major in vivo requires Pten in macrophages. Eur. J. Immunol. 38: 1331-1340.
19. Fukao, T., M. Tanabe, Y. Terauchi, T. Ota, S. Matsuda, T. Asano, T. Kadowaki, T. Takeuchi, and S. Koyasu. 2002. PI3K-mediated negative feedback regulation of IL-12 production in DCs. Nat. Immunol. 3: 875-881.
20. Okkenhaug, K., A. Bilancio, G. Farjot, H. Priddle, S. Sancho, E. Peskett, W. Pearce, S. E. Meek, A. Salpekar, M. D. Waterfield, et al. 2002. Impaired B and T cell antigen receptor signaling in p110δ PI 3-kinase mutant mice. Science 297: 1031-1034.
21. Okkenhaug, K., D. T. Patton, A. Bilancio, F. Garcon, W. C. Rowan, and B. Vanhaesebroeck. 2006. The p110δ isoform of phosphoinositide 3-kinase controls clonal expansion and differentiation of Th cells. J. Immunol. 177: 5122-5128. (Pubitemid 44527583)
22. Nashed, B. F., T. Zhang, M. Al-Alwan, G. Srinivasan, A. J. Halayko, K. Okkenhaug, B. Vanhaesebroeck, K. T. Hayglass, and A. J. Marshall. 2007. Role of the phosphoinositide 3-kinase p110δ in generation of type 2 cytokine responses and allergic airway inflammation. Eur. J. Immunol. 37: 416-424.
23. Savitsky, D., and K. Calame. 2006. B-1 B lymphocytes require Blimp-1 for immunoglobulin secretion. J. Exp. Med. 203: 2305-2314.
24. Aebischer, T., S. F. Moody, and E. Handman. 1993. Persistence of virulent Leishmania major in murine cutaneous leishmaniasis: a possible hazard for the host. Infect. Immun. 61: 220-226. (Pubitemid 23015420)
25. Uzonna, J. E., and P. A. Bretscher. 2001. Anti-IL-4 antibody therapy causes regression of chronic lesions caused by medium-dose Leishmania major infection in BALB/c mice. Eur. J. Immunol. 31: 3175-3184.
26. + lymphocytes in vivo during healing and progressive murine leishmaniasis. Proc. Natl. Acad. Sci. USA 88: 7011-7015.
27. Poulter, L. W., and C. R. Pandolph. 1982. Mechanisms of immunity to leishmaniasis, IV: Significance of lymphatic drainage from the site of infection. Clin. Exp. Immunol. 48: 396-402.
28. + T cells are required for primary immunity in C57BL/6 mice following low-dose, intradermal challenge with Leishmania major. J. Immunol. 168: 3992-4000.
29. Okkenhaug, K., and B. Vanhaesebroeck. 2003. PI3K-signalling in B- and T-cells: insights from gene-targeted mice. Biochem. Soc. Trans. 31: 270-274. (Pubitemid 36241443)
30. Bilancio, A., K. Okkenhaug, M. Camps, J. L. Emery, T. Ruckle, C. Rommel, and B. Vanhaesebroeck. 2006. Key role of the p110δ isoform of PI3K in B-cell antigen and IL-4 receptor signaling: comparative analysis of genetic and pharmacologic interference with p110δ function in B cells. Blood 107: 642-650.
31. Miles, S. A., S. M. Conrad, R. G. Alves, S. M. Jeronimo, and D. M. Mosser. 2005. A role for IgG immune complexes during infection with the intracellular pathogen Leishmania. J. Exp. Med. 201: 747-754.
32. Buxbaum, L. U., and P. Scott. 2005. Interleukin 10- and Fcγ receptor-deficient mice resolve Leishmania mexicana lesions. Infect. Immun. 73: 2101-2108.
33. Woelbing, F., S. L. Kostka, K. Moelle, Y. Belkaid, C. Sunderkoetter, S. Verbeek, A. Waisman, A. P. Nigg, J. Knop, M. C. Udey, and E. von Stebut. 2006. Uptake of Leishmania major by dendritic cells is mediated by Fcγ receptors and facilitates acquisition of protective immunity. J. Exp. Med. 203: 177-188.
34. + T cells are important for the balance between protective and pathogenic cell-mediated immunity. J. Exp. Med. 179: 589-600.
35. Belkaid, Y., and B. T. Rouse. 2005. Natural regulatory T cells in infectious disease. Nat Immunol. 6: 353-360.
36. + regulatory T cells control autoimmunity? Curr. Opin. Immunol. 17: 638-642.
37. Chang, X., P. Zheng, and Y. Liu. 2006. FoxP3: a genetic link between immunodeficiency and autoimmune diseases. Autoimmun. Rev. 5: 399-402.
38. Kallies, A., E. D. Hawkins, G. T. Belz, D. Metcalf, M. Hommel, L. M. Corcoran, P. D. Hodgkin, and S. L. Nutt. 2006. Transcriptional repressor Blimp-1 is essential for T cell homeostasis and self-tolerance. Nat. Immunol. 7: 466-474.
39. Martins, G. A., L. Cimmino, M. Shapiro-Shelef, M. Szabolcs, A. Herron, E. Magnusdottir, and K. Calame. 2006. Transcriptional repressor Blimp-1 regulates T cell homeostasis and function. Nat. Immunol. 7: 457-465.
40. Locksley, R. M., and P. Scott. 1991. Helper T-cell subsets in mouse leishmaniasis: induction, expansion and effector function. Immunol. Today 12: A58-A61.
41. Reiner, S. L., and R. A. Seder. 1995. T helper cell differentiation in immune response. Curr. Opin. Immunol. 7: 360-366.
42. Uzonna, J. E., G. F. Spath, S. M. Beverley, and P. Scott. 2004. Vaccination with phosphoglycan-deficient Leishmania major protects highly susceptible mice from virulent challenge without inducing a strong Th1 response. J. Immunol. 172: 3793-3797.
43. Anderson, C. F., S. Mendez, and D. L. Sacks. 2005. Nonhealing infection despite Th1 polarization produced by a strain of Leishmania major in C57BL/6 mice. J. Immunol. 174: 2934-2941.
44. + T cells and accompanied by overproduction of IL-12, IFN-γ and TNF-α. J. Immunol. 157: 798-805.
45. Uzonna, J. E., R. S. Kaushik, J. R. Gordon, and H. Tabel. 1998. Experimental murine Trypanosoma congolense infections, I: Administration of anti-IFN-γ antibodies alters trypanosome-susceptible mice to a resistant-like phenotype. J. Immunol. 161: 5507-5515.
46. Shi, M., W. Pan, and H. Tabel. 2003. Experimental African trypanosomiasis: IFN-γ mediates early mortality. Eur. J. Immunol. 33: 108-118.
47. + T cells mediates early mortality in highly susceptible mice. J. Immunol. 176: 1724-1732.
48. Theron, M., K. J. Huang, Y. W. Chen, C. C. Liu, and H. Y. Lei. 2005. A probable role for IFN-γ in the development of a lung immunopathology in SARS. Cytokine 32: 30-38.
49. + T cells during infection with respiratory syncytial virus are mediated by IFN-γ. Eur. J. Immunol. 32: 2117-2123.
50. + regulatory T cells correlates with more rapid parasite growth in human malaria infection. Immunity 23: 287-296.
51. + T cells in skin lesions of patients with cutaneous leishmaniasis exhibit phenotypic and functional characteristics of natural regulatory T cells. J. Infect. Dis. 193: 1313-1322.
52. + regulatory T cells in reactivation of persistent leishmaniasis and control of concomitant immunity. J. Exp. Med. 200: 201-210.
53. - Th1 cells are the major source of host-protective regulatory IL-10 during intracellular protozoan infection. J. Exp. Med. 204: 273-283.
54. Lin, L., J. D. Hron, and S. L. Peng. 2004. Regulation of NF-κB, Th activation, and autoinflammation by the forkhead transcription factor Foxo3a. Immunity 21: 203-213.
55. Lin, L., M. S. Spoor, A. J. Gerth, S. L. Brody, and S. L. Peng. 2004. Modulation of Th1 activation and inflammation by the NF-κB repressor Foxj1. Science 303: 1017-1020.
56. Lee, K. S., H. K. Lee, J. S. Hayflick, Y. C. Lee, and K. D. Puri. 2006. Inhibition of phosphoinositide 3-kinase δ attenuates allergic airway inflammation and hyperresponsiveness in murine asthma model. FASEB J. 20: 455-465.
57. Jackson, S. F., and S. M. Schoenwaelder. 2006. Type I phosphoinositide 3-kinases: potential antithrombotic targets? Cell. Mol. Life Sci. 63: 1085-1090.
58. Fruman, D. A. 2007. The role of class I phosphoinositide 3-kinase in T-cell function and autoimmunity. Biochem. Soc. Trans. 35: 177-180.
59. Rommel, C., M. Camps, and H. Ji. 2007. PI3Kδ and PI3Kγ: partners in crime in inflammation in rheumatoid arthritis and beyond? Nat. Rev. Immunol. 7: 191-201.
60. Grogl, M., T. N. Thomason, and E. D. Franke. 1992. Drug resistance in leishmaniasis: its implications in systemic chemotherapy of cutaneous and mucocutaneous disease. Am. J. Trop. Med. Hyg. 47: 117-126.