Blocking Junctional Adhesion Molecule C Enhances Dendritic Cell Migration and Boosts the Immune Responses against

English version České info

Leishmaniasis is a parasitic disease transmitted to humans through sand fly bites. Clinical symptoms vary from self-healing cutaneous lesions to death. Cutaneous leishmaniasis is particularly studied in mice inoculated with Leishmania major. In this model, some strains (e.g. C57BL/6) are resistant due to a Th1 immune response promoting parasite killing. Conversely, other strains (e.g. BALB/c) are susceptible due to a nonprotective Th2 response. DCs are professional antigen-presenting cells that educate antigen-specific T cells. Improving the migration of DCs from the site of infection to the lymph nodes, where T cells reside, may improve the T cell response. JAM-C is a vascular adhesion molecule implicated in leukocyte migration in different inflammatory models. We found that JAM-C blockade with antibodies increases vascular permeability and consequently improves the migration of DCs to sites of infection and draining lymph nodes. This increased leukocyte migration boosted the induction of the Th1 response in resistant mice, while in susceptible mice the Th2 response was augmented. This led to disease improvement or exacerbation, respectively. Our results illustrate the key role of a vascular adhesion molecule in controlling leukocyte migration and the subsequent immune events in response to pathogen infections.

Vyšlo v časopise: Blocking Junctional Adhesion Molecule C Enhances Dendritic Cell Migration and Boosts the Immune Responses against. PLoS Pathog 10(12): e32767. doi:10.1371/journal.ppat.1004550
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004550

Souhrn

Zdroje

1. MurrayHW, BermanJD, DaviesCR, SaraviaNG (2005) Advances in leishmaniasis. The Lancet 366 : 1561–1577.

2. KayeP, ScottP (2011) Leishmaniasis: complexity at the host-pathogen interface. Nat Rev Microbiol 9 : 604–615.

3. SacksD, Noben-TrauthN (2002) The immunology of susceptibility and resistance to Leishmania major in mice. Nat Rev Immunol 2 : 845–858.

4. HeinzelF, SadickM, MuthaS, LocksleyR (1991) Production of interferon-gamma, interleukin-2, interleukin-4, and interleukin-10 by CD4+ lymphocytes in vivo during healing and progressive murine leishmaniasis. PNAS 88 : 7011–7015.

5. WangZE, ReinerLR, ZhengS, DaltonDK, LockleyRM (1994) CD4 + Effector Cells Default to the Th2 Pathway in Interferon y-deficient Mice Infected with Leishmania major. J Exp Med 179 : 1367–1371.

6. LiewF, MillottS, ParkinsonC, PalmerR, MoncadaS (1990) Macrophages killing of Leishmania parasite in vivo is mediated by nitric oxide from L-arginine. J Immunol 144 : 4794–4797.

7. Tacchini-CottierF, WeinkopffT, LaunoisP (2012) Does T Helper Differentiation Correlate with Resistance or Susceptibility to Infection with L. major? Some Insights From the Murine Model. Front Immunol 3 : 32.

8. NgLG, HsuA, MandellMA, RoedigerB, HoellerC, et al. (2008) Migratory dermal dendritic cells act as rapid sensors of protozoan parasites. PLoS Pathog 4: e1000222.

9. Von StebutE, BelkaidY, JakobT, SacksD, UdeyM (1998) Uptake of Leishmania major Amastigotes Results in Activation and Interleukin 12 Release from Murine Skin–derived Dendritic Cells: Implications for the Initiation of Anti-Leishmania Immunity. J Exp Med 188 : 1547–1552.

10. LeonB, Lopez-BravoM, ArdavinC (2007) Monocyte-derived dendritic cells formed at the infection site control the induction of protective T helper 1 responses against Leishmania. Immunity 26 : 519–531.

11. De TrezC, MagezS, AkiraS, RyffelB, CarlierY, et al. (2009) iNOS-producing inflammatory dendritic cells constitute the major infected cell type during the chronic Leishmania major infection phase of C57BL/6 resistant mice. PLoS Pathog 5: e1000494.

12. SatoN, AhujaSK, QuinonesM, KosteckiV, ReddickRL, et al. (2000) CC Chemokine Receptor (CCR)2 Is Required for Langerhans Cell Migration and Localization of T Helper Cell Type 1 (Th1)-inducing Dendritic Cells: Absence of CCR2 Shifts the Leishmania major–resistant Phenotype to a Susceptible State Dominated by Th2 Cytokines, B Cell Outgrowth, and Sustained Neutrophilic Inflammation. J Exp Med 192 : 205–218.

13. LeyK, LaudannaC, CybulskyMI, NoursharghS (2007) Getting to the site of inflammation: the leukocyte adhesion cascade updated. Nat Rev Immunol 7 : 678–689.

14. ScheiermannC, ColomB, MedaP, PatelNS, VoisinMB, et al. (2009) Junctional adhesion molecule-C mediates leukocyte infiltration in response to ischemia reperfusion injury. Arterioscler Thromb Vasc Biol 29 : 1509–1515.

15. LiangT, ChiuH, GurneyA, SidleA, TumasD, et al. (2002) Vascular Endothelial-Junctional Adhesion Molecule (VE-JAM)/JAM 2 Interacts with T, NK, and Dendritic Cells Through JAM 3. J Immunol 168 : 1618–1626.

16. SantosoS, SachsUJH, KrollH, LinderM, RufA, et al. (2002) The Junctional Adhesion Molecule 3 (JAM-3) on Human Platelets is a Counterreceptor for the Leukocyte Integrin Mac-1. J Exp Med 196 : 679–691.

17. ZenK, BabbinBA, LiuY, WhelanJB, NusratA, et al. (2004) JAM-C is a component of desmosomes and a ligand for CD11b/CD18-mediated neutrophil transepithelial migration. Mol Biol Cell 15 : 3926–3937.

18. MorrisAP, TawilA, BerkovaZ, WibleL, SmithCW, et al. (2006) Junctional Adhesion Molecules (JAMs) are differentially expressed in fibroblasts and co-localize with ZO-1 to adherens-like junctions. Cell Commun Adhes 13 : 233–247.

19. ScheiermannC, MedaP, Aurrand-LionsM, MadaniR, YiangouY, et al. (2007) Expression and function of junctional adhesion molecule-C in myelinated peripheral nerves. Science 318 : 1472–1475.

20. LamagnaC, MedaP, MandicourtG, BrownJ, GilbertRJ, et al. (2005) Dual interaction of JAM-C with JAM-B and alpha(M)beta2 integrin: function in junctional complexes and leukocyte adhesion. Mol Biol Cell 16 : 4992–5003.

21. CunninghamSA, RodriguezJM, ArrateMP, TranTM, BrockTA (2002) JAM2 interacts with alpha4beta1. Facilitation by JAM3. J Biol Chem 277 : 27589–27592.

22. Aurrand-LionsM, DuncanL, BallestremC, ImhofBA (2001) JAM-2, a novel immunoglobulin superfamily molecule, expressed by endothelial and lymphatic cells. J Biol Chem 276 : 2733–2741.

23. BradfieldPF, ScheiermannC, NoursharghS, OdyC, LuscinskasFW, et al. (2007) JAM-C regulates unidirectional monocyte transendothelial migration in inflammation. Blood 110 : 2545–2555.

24. WoodfinA, VoisinMB, BeyrauM, ColomB, CailleD, et al. (2011) The junctional adhesion molecule JAM-C regulates polarized transendothelial migration of neutrophils in vivo. Nat Immunol 12 : 761–769.

25. VestweberD (2012) Relevance of endothelial junctions in leukocyte extravasation and vascular permeability. Ann N Y Acad Sci 1257 : 184–192.

26. CharmoyM, Brunner-AgtenS, AebischerD, AudersetF, LaunoisP, et al. (2010) Neutrophil-derived CCL3 is essential for the rapid recruitment of dendritic cells to the site of Leishmania major inoculation in resistant mice. PLoS Pathog 6: e1000755.

27. Ribeiro-GomesFL, PetersNC, DebrabantA, SacksDL (2012) Efficient capture of infected neutrophils by dendritic cells in the skin inhibits the early anti-leishmania response. PLoS Pathog 8: e1002536.

28. MilesAA, MilesEM (1952) Vascular reactions to histamine, histamine-liberator and leukotaxine in the skin of guinea-pigs. J Physiol 118 : 228–257.

29. RobbianiDF, FinchRA, JagerD, MullerWA, SartorelliAC, et al. (2000) The Leukotriene C4 Transporter MRP1 Regulates CCL19 (MIP-3b, ELC)–Dependent Mobilization of Dendritic Cells to Lymph Nodes. Cell 103 : 757–768.

30. Aurrand-LionsM, Johnson-LegerC, WongC, Du PasquierL, ImhofB (2001) Heterogeneity of endothelial junctions is reflected by differential expression and specific subcellular localization of the three JAM family members. Blood 98 : 3699–3707.

31. LamagnaC, Hodivala-DilkeKM, ImhofBA, Aurrand-LionsM (2005) Antibody against Junctional Adhesion Molecule-C Inhibits Angiogenesis and Tumor Growth. Cancer Res 65 : 5703–5710.

32. LiX, StankovicM, LeeBP, Aurrand-LionsM, HahnCN, et al. (2009) JAM-C induces endothelial cell permeability through its association and regulation of {beta}3 integrins. Arterioscler Thromb Vasc Biol 29 : 1200–1206.

33. TenanM, Aurrand-LionsM, WidmerV, AlimentiA, BurkhardtK, et al. (2010) Cooperative expression of junctional adhesion molecule-C and -B supports growth and invasion of glioma. Glia 58 : 524–537.

34. OrlovaVV, EconomopoulouM, LupuF, SantosoS, ChavakisT (2006) Junctional adhesion molecule-C regulates vascular endothelial permeability by modulating VE-cadherin-mediated cell-cell contacts. J Exp Med 203 : 2703–2714.

35. SpindlerV, SchlegelN, WaschkeJ (2010) Role of GTPases in control of microvascular permeability. Cardiovasc Res 87 : 243–253.

36. GoddardLM, Iruela-ArispeML (2013) Cellular and molecular regulation of vascular permeability. Thromb Haemost 109 : 407–415.

37. WesselF, WinderlichM, HolmM, FryeM, Rivera-GaldosR, et al. (2014) Leukocyte extravasation and vascular permeability are each controlled in vivo by different tyrosine residues of VE-cadherin. Nat Immunol

38. PetersNC, EgenJG, SecundinoN, DebrabantA, KimblinN, et al. (2008) In Vivo Imaging Reveals an Essential Role for Neutrophils in Leishmaniasis Transmitted by Sand Flies. Science 321 : 970–974.

39. Tacchini-CottierF, ZweifelC, BelkaidY, MukankundiyeC, VaseiM, et al. (2000) An Immunomodulatory Function for Neutrophils During the Induction of a CD4 + Th2 Response in BALB/c Mice Infected with Leishmania major. J Immunol 165 : 2628–2636.

40. LimaGM, VallochiAL, SilvaUR, BevilacquaEM, KifferMM, et al. (1998) The role of polymorphonuclear leukocytes in the resistance to cutaneous Leishmaniasis. Immunol Lett 64 : 145–151.

41. Ribeiro-GomesFL, OteroAC, GomesNA, Moniz-de-SouzaMCA, FinkelsteinLC, et al. (2004) Macrophage Interactions with Neutrophils Regulate Leishmania major Infection. J Immunol 172 : 4454–4462.

42. ChenL, ZhangZH, WatanabeT, YamashitaT, KobayakawaT, et al. (2005) The involvement of neutrophils in the resistance to Leishmania major infection in susceptible but not in resistant mice. Parasitol Int 54 : 109–118.

43. SerbinaNV, PamerEG (2006) Monocyte emigration from bone marrow during bacterial infection requires signals mediated by chemokine receptor CCR2. Nat Immunol 7 : 311–317.

44. BalukP, FuxeJ, HashizumeH, RomanoT, LashnitsE, et al. (2007) Functionally specialized junctions between endothelial cells of lymphatic vessels. J Exp Med 204 : 2349–2362.

45. PflickeH, SixtM (2009) Preformed portals facilitate dendritic cell entry into afferent lymphatic vessels. J Exp Med 206 : 2925–2935.

46. ZimmerliC, LeeBP, PalmerG, GabayC, AdamsRH, et al. (2009) Adaptive Immune Response in JAM-C-Deficient Mice: Normal Initiation but Reduced IgG Memory. J Immunol 182 : 4728–4736.

47. ZaphC, ScottP (2003) Th1 Cell-Mediated Resistance to Cutaneous Infection with Leishmania major Is Independent of P -⁠ and E-Selectins. The Journal of Immunology 171 : 4726–4732.

48. KropfP, KadolskyUD, RogersM, ClokeTE, MüllerI (2010) The Leishmaniasis Model. Methods in Microbiology 37 : 307–328.