Hostname: page-component-7479d7b7d-q6k6v Total loading time: 0 Render date: 2024-07-10T10:08:18.607Z Has data issue: false hasContentIssue false
  • English
  • Français

Human dendritic cell sequestration onto the Necator americanus larval sheath during ex-sheathing: a possible mechanism for immune privilege

Published online by Cambridge University Press:  19 February 2018

A. Hassan ,
D. I. Pritchard  and
A. M. Ghaemmaghami Open the ORCID record for A. M. Ghaemmaghami [Opens in a new window]
A. Hassan
Affiliation:
Division of Immunology, School of Life Sciences, Faculty of Medicine & Health Sciences, Nottingham NG7 2RD, UK
D. I. Pritchard
Affiliation:
School of Pharmacy, University of Nottingham, Nottingham NG7 2RD, UK
A. M. Ghaemmaghami*
Affiliation:
Division of Immunology, School of Life Sciences, Faculty of Medicine & Health Sciences, Nottingham NG7 2RD, UK
*
Author for correspondence: A.M. Ghaemmaghami, E-mail: amir.ghaemmaghami@nottingham.ac.uk
Get access Rights & Permissions [Opens in a new window]

Abstract

Despite the profound health implications of Necator americanus infection in humans, many aspects of its interaction with the host immune system are poorly understood. Here we investigated the early events at the interface of N. americanus larvae (L3) and human dendritic cells (DCs). Our data show that co-culturing DCs and the larvae trigger ex-sheathing of hookworms rapidly where a majority of DCs are sequestered onto the larval sheath allowing the ex-sheathed larvae to migrate away unchallenged. Intriguingly, DCs show negligible interaction with the ex-sheathed larvae, alluding to differences between the surface chemistry of the larva and its sheath. Furthermore, blocking of two key C-type lectin receptors on DC surface (i.e. DC-SIGN and mannose receptor) resulted in inhibition of ex-sheathing process and DC sequestration, highlighting the importance of C-type lectins on DCs in the induction of the ex-sheathing. Analyses of DC phenotype and cytokine profile after co-culture with the N. americanus larvae showed an immature phenotype as evidenced by the low expression of the maturation markers and cytokines. These data provide new insights into early events at the interface of human DCs and N. americanus larvae and could explain how L3 evade immune recognition upon initial interaction with DCs.

Keywords

C-type lectin receptorsdendritic cellsexsheathmenthookwormimmune evasionimmune modulationlarval sheathmannose receptorNecator americanus
Type
Research Article
Information
Parasitology , Volume 145 , Issue 9 , August 2018 , pp. 1183 - 1190
Check for updates
Copyright
Copyright © Cambridge University Press 2018 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Chau, DY, Johnson, C, Macneil, S, Haycock, JW and Ghaemmaghami, AM (2013) The development of a 3D immunocompetent model of human skin. Biofabrication 5, 035011.Google Scholar
Emara, M, Royer, PJ, Abbas, Z, Sewell, HF, Mohamed, GG, Singh, S, Peel, S, Fox, J, Shakib, F, Martinez-Pomares, L and Ghaemmaghami, AM (2011) Recognition of the major cat allergen Fel d 1 through the cysteine-rich domain of the mannose receptor determines its allergenicity. Journal of Biological Chemistry 286, 13033–13040.Google Scholar
Emara, M, Royer, PJ, Mahdavi, J, Shakib, F and Ghaemmaghami, AM (2012) Retagging identifies dendritic cell-specific intercellular adhesion molecule-3 (ICAM3)-grabbing non-integrin (DC-SIGN) protein as a novel receptor for a major allergen from house dust mite. Journal of Biological Chemistry 287, 5756–5763.Google Scholar
Everts, B, Hussaarts, L., Driessen, NN, Meevissen, MH, Schramm, G, Van Der Ham, AJ, Van Der Hoeven, B, Scholzen, T, Burgdorf, S, Mohrs, M, Pearce, EJ, Hokke, CH, Haas, H, Smits, HH and Yazdanbakhsh, M (2012) Schistosome-derived omega-1 drives Th2 polarization by suppressing protein synthesis following internalization by the mannose receptor. Journal of Experimental Medicine 209, 17531–67, s1.Google Scholar
Garcia-Nieto, S, Johal, RK, Shakesheff, KM, Emara, M, Royer, PJ, Chau, DY, Shakib, F and Ghaemmaghami, AM (2010) Laminin and fibronectin treatment leads to generation of dendritic cells with superior endocytic capacity. PLoS ONE 5, e10123.Google Scholar
Garcia-Vallejo, JJ and Van Kooyk, Y (2013) The physiological role of DC-SIGN: a tale of mice and men. Trends in Immunology 34, 482–486.Google Scholar
Geiger, SM, Caldas, IR, Mc Glone, BE, Campi-Azevedo, AC, De Oliveira, LM, Brooker, S, Diemert, D, Correa-Oliveira, R and Bethony, JM (2007) Stage-specific immune responses in human Necator americanus infection. Parasite Immunology 29, 347–358.Google Scholar
Geijtenbeek, TB, Engering, A and Van Kooyk, Y (2002) DC-SIGN, a C-type lectin on dendritic cells that unveils many aspects of dendritic cell biology. Journal of Leukocyte Biology 71, 921–931.Google Scholar
Hawdon, JM, Volk, SW, Rose, R, Pritchard, DI, Behnke, JM and Schad, GA (1993) Observations on the feeding behaviour of parasitic third-stage hookworm larvae. Parasitology 106(Pt 2), 163–169.Google Scholar
Heuze, ML, Vargas, P, Chabaud, M, Le Berre, M, Liu, YJ, Collin, O, Solanes, P, Voituriez, R, Piel, M and Lennon-Dumenil, AM (2013) Migration of dendritic cells: physical principles, molecular mechanisms, and functional implications. Immunological Reviews 256, 240–254.Google Scholar
Hotez, PJ, Brindley, PJ, Bethony, JM, King, CH, Pearce, EJ and Jacobson, J (2008) Helminth infections: the great neglected tropical diseases. The Journal of Clinical Investigation 118, 1311–1321.Google Scholar
Imai, K, Minamiya, Y, Koyota, S, Ito, M, Saito, H, Sato, Y, Motoyama, S, Sugiyama, T and Ogawa, J-I (2012) Inhibition of dendritic cell migration by transforming growth factor-β1 increases tumor-draining lymph node metastasis. Journal of Experimental & Clinical Cancer Research: CR 31, 3–3.Google Scholar
Kumar, S and Pritchard, DI (1992a) Distinction of human hookworm larvae based on lectin-binding characteristics. Parasite Immunology 14, 233–237.Google Scholar
Kumar, S and Pritchard, DI (1992b) Skin penetration by ensheathed third-stage infective larvae of Necator americanus, and the host's immune response to larval antigens. International Journal for Parasitology 22, 573–579.Google Scholar
Kumar, S, Laouar, L, Pritchard, DI and Lowe, KC (1992) A novel method for the isolation of nematode larvae using pluronic F-68-treated cellulose strips. Journal of Parasitology 78, 550–552.Google Scholar
Loukas, A and Prociv, P (2001) Immune responses in hookworm infections. Clinical Microbiology Reviews 14, 689–703, table of contents.Google Scholar
Ludwig, IS, Lekkerkerker, AN, Depla, E, Bosman, F, Musters, RJP, Depraetere, S, Van Kooyk, Y and Geijtenbeek, TBH (2004) Hepatitis C virus targets DC-SIGN and L-SIGN To escape lysosomal degradation. Journal of Virology 78, 8322–8332.Google Scholar
Martin-Fontecha, A, Lanzavecchia, A and Sallusto, F (2009) Dendritic cell migration to peripheral lymph nodes. Handbook of Experimental Pharmacology 188, 31–49.Google Scholar
Matthews, BE (1982) Skin penetration by Necator americanus larvae. Zeitschrift Fur Parasitenkunde 68, 81–86.Google Scholar
Pasuralertsakul, S and Ngrenngarmlert, W (2006) The exsheathment of Necator americanus infective larvae. Southeast Asian Journal of Tropical Medicine and Public Health 37(Suppl. 3), 28–31.Google Scholar
Quinnell, RJ, Pritchard, DI, Raiko, A, Brown, AP and Shaw, MA (2004) Immune responses in human necatoriasis: association between interleukin-5 responses and resistance to reinfection. Journal of Infectious Diseases 190, 430–438.Google Scholar
Royer, PJ, Emara, M, Yang, C, Al-Ghouleh, A, Tighe, P, Jones, N, Sewell, HF, Shakib, F, Martinez-Pomares, L and Ghaemmaghami, AM (2010) The mannose receptor mediates the uptake of diverse native allergens by dendritic cells and determines allergen-induced T cell polarization through modulation of IDO activity. Journal of Immunology 185, 1522–1531.Google Scholar
Salazar, F, Sewell, HF, Shakib, F and Ghaemmaghami, AM (2013) The role of lectins in allergic sensitization and allergic disease. Journal of Allergy and Clinical Immunology 132, 27–36.Google Scholar
Salazar, F, Hall, L, Negm, OH, Awuah, D, Tighe, PJ, Shakib, F and Ghaemmaghami, AM (2016) The mannose receptor negatively modulates the toll-like receptor 4-aryl hydrocarbon receptor-indoleamine 2,3-dioxygenase axis in dendritic cells affecting T helper cell polarization. Journal of Allergy and Clinical Immunology 137, 1841–1851 e2.Google Scholar
Savina, A and Amigorena, S (2007) Phagocytosis and antigen presentation in dendritic cells. Immunological Reviews 219, 143–156.Google Scholar
Smith-Garvin, JE, Koretzky, GA and Jordan, MS (2009) T cell activation. Annual Review of Immunology 27, 591–619.Google Scholar
Thompson, MR, Kaminski, JJ, Kurt-Jones, EA and Fitzgerald, KA (2011) Pattern recognition receptors and the innate immune response to viral infection. Viruses 3, 920–940.Google Scholar
Van Kooyk, Y and Geijtenbeek, TBH (2003) DC-SIGN: escape mechanism for pathogens. Nature Reviews. Immunology 3, 697–709.Google Scholar
Wollenberg, A, Mommaas, M, Oppel, T, Schottdorf, EM, Gunther, S and Moderer, M (2002) Expression and function of the mannose receptor CD206 on epidermal dendritic cells in inflammatory skin diseases. The Journal of Investigative Dermatology 118, 327–334.Google Scholar

Hassan et al. supplementary material

Hassan et al. supplementary material 1

Download Hassan et al. supplementary material(Video)
Video 180.7 MB