Controlled human hookworm infection remodels plasmacytoid dendritic cells and regulatory T cells towards profiles seen in natural infections in endemic areas.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
16 Jul 2024
16 Jul 2024
Historique:
received:
11
01
2023
accepted:
08
07
2024
medline:
17
7
2024
pubmed:
17
7
2024
entrez:
16
7
2024
Statut:
epublish
Résumé
Hookworm infection remains a significant public health concern, particularly in low- and middle-income countries, where mass drug administration has not stopped reinfection. Developing a vaccine is crucial to complement current control measures, which necessitates a thorough understanding of host immune responses. By leveraging controlled human infection models and high-dimensional immunophenotyping, here we investigated the immune remodeling following infection with 50 Necator americanus L3 hookworm larvae in four naïve volunteers over two years of follow-up and compared the profiles with naturally infected populations in endemic areas. Increased plasmacytoid dendritic cell frequency and diminished responsiveness to Toll-like receptor 7/8 ligand were observed in both controlled and natural infection settings. Despite the increased CD45RA
Identifiants
pubmed: 39013877
doi: 10.1038/s41467-024-50313-0
pii: 10.1038/s41467-024-50313-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
5960Subventions
Organisme : Stichting Dioraphte (Dioraphte Foundation)
ID : 18040403
Informations de copyright
© 2024. The Author(s).
Références
Loukas, A., Maizels, R. M. & Hotez, P. J. The yin and yang of human soil-transmitted helminth infections. Int J. Parasitol. 51, 1243–1253 (2021).
pubmed: 34774540
pmcid: 9145206
doi: 10.1016/j.ijpara.2021.11.001
Jia, T.-W., Melville, S., Utzinger, J., King, C. H. & Zhou, X.-N. Soil-Transmitted Helminth Reinfection after Drug Treatment: A Systematic Review and Meta-Analysis. PLOS Neglected Tropical Dis. 6, e1621 (2012).
doi: 10.1371/journal.pntd.0001621
Keiser, J. & Utzinger, J. Efficacy of current drugs against soil-transmitted helminth infections: systematic review and meta-analysis. JAMA 299, 1937–1948 (2008).
pubmed: 18430913
doi: 10.1001/jama.299.16.1937
de Jong, S. E. et al. Systems analysis and controlled malaria infection in Europeans and Africans elucidate naturally acquired immunity. Nat. Immunol. 22, 654–665 (2021).
pubmed: 33888898
doi: 10.1038/s41590-021-00911-7
Sandoval, D. M. et al. Adaptive T cells regulate disease tolerance in human malaria. medRxiv, 2021.2008.2019.21262298, https://doi.org/10.1101/2021.08.19.21262298 (2021).
Chapman, P. R., Giacomin, P., Loukas, A. & McCarthy, J. S. Experimental human hookworm infection: a narrative historical review. PLOS Neglected Tropical Dis. 15, e0009908 (2021).
doi: 10.1371/journal.pntd.0009908
Gaze, S. et al. Characterising the mucosal and systemic immune responses to experimental human hookworm infection. PLoS Pathog. 8, e1002520 (2012).
pubmed: 22346753
pmcid: 3276555
doi: 10.1371/journal.ppat.1002520
Geiger, S. M., Fujiwara, R. T., Santiago, H., Corrêa-Oliveira, R. & Bethony, J. M. Early stage-specific immune responses in primary experimental human hookworm infection. Microbes Infect. 10, 1524–1535 (2008).
pubmed: 18848637
doi: 10.1016/j.micinf.2008.09.003
Hoogerwerf, M. A. et al. New Insights Into the Kinetics and Variability of Egg Excretion in Controlled Human Hookworm Infections. J. Infect. Dis. 220, 1044–1048 (2019).
pubmed: 31077279
doi: 10.1093/infdis/jiz218
de Ruiter, K. et al. Helminth infections drive heterogeneity in human type 2 and regulatory cells. Sci. Transl. Med. 12, eaaw3703 (2020).
pubmed: 31894102
doi: 10.1126/scitranslmed.aaw3703
Smith, K. A. et al. Low-level regulatory T-cell activity is essential for functional type-2 effector immunity to expel gastrointestinal helminths. Mucosal. Immunol. 9, 428–443 (2016).
pubmed: 26286232
doi: 10.1038/mi.2015.73
Taylor, M. D. et al. Removal of regulatory T cell activity reverses hyporesponsiveness and leads to filarial parasite clearance in vivo. J. Immunol. 174, 4924–4933 (2005).
pubmed: 15814720
doi: 10.4049/jimmunol.174.8.4924
Faget, J. et al. ICOS-ligand expression on plasmacytoid dendritic cells supports breast cancer progression by promoting the accumulation of immunosuppressive CD4+ T cells. Cancer Res. 72, 6130–6141 (2012).
pubmed: 23026134
doi: 10.1158/0008-5472.CAN-12-2409
Dann, E., Henderson, N. C., Teichmann, S. A., Morgan, M. D. & Marioni, J. C. Differential abundance testing on single-cell data using k-nearest neighbor graphs. Nat. Biotechnol. 40, 245–253 (2022).
pubmed: 34594043
doi: 10.1038/s41587-021-01033-z
Wang, J., Ioan-Facsinay, A., van der Voort, E. I., Huizinga, T. W. & Toes, R. E. Transient expression of FOXP3 in human activated nonregulatory CD4+ T cells. Eur. J. Immunol. 37, 129–138 (2007).
pubmed: 17154262
doi: 10.1002/eji.200636435
Miyara, M. et al. Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FoxP3 transcription factor. Immunity 30, 899–911 (2009).
pubmed: 19464196
doi: 10.1016/j.immuni.2009.03.019
Moon, K. R. et al. Visualizing structure and transitions in high-dimensional biological data. Nat. Biotechnol. 37, 1482–1492 (2019).
pubmed: 31796933
pmcid: 7073148
doi: 10.1038/s41587-019-0336-3
Yang, J. et al. Antigen-Specific T Cell Analysis Reveals That Active Immune Responses to beta Cell Antigens Are Focused on a Unique Set of Epitopes. J. Immunol. 199, 91–96 (2017).
pubmed: 28550202
doi: 10.4049/jimmunol.1601570
Loukas, A. et al. Hookworm infection. Nat. Rev. Dis. Prim. 2, 16088 (2016).
pubmed: 27929101
doi: 10.1038/nrdp.2016.88
Maizels, R. M., Smits, H. H. & McSorley, H. J. Modulation of Host Immunity by Helminths: The Expanding Repertoire of Parasite Effector Molecules. Immunity 49, 801–818 (2018).
pubmed: 30462997
pmcid: 6269126
doi: 10.1016/j.immuni.2018.10.016
Ye, Y., Gaugler, B., Mohty, M. & Malard, F. Plasmacytoid dendritic cell biology and its role in immune-mediated diseases. Clin. Transl. Immunol. 9, e1139 (2020).
doi: 10.1002/cti2.1139
Gregorio, J. et al. Plasmacytoid dendritic cells sense skin injury and promote wound healing through type I interferons. J. Exp. Med. 207, 2921–2930 (2010).
pubmed: 21115688
pmcid: 3005239
doi: 10.1084/jem.20101102
Ogata, M. et al. Plasmacytoid dendritic cells have a cytokine-producing capacity to enhance ICOS ligand-mediated IL-10 production during T-cell priming. Int. Immunol. 25, 171–182 (2012).
pubmed: 23125331
doi: 10.1093/intimm/dxs103
Ito, T. et al. Plasmacytoid dendritic cells prime IL-10–producing T regulatory cells by inducible costimulator ligand. J. Exp. Med. 204, 105–115 (2007).
pubmed: 17200410
pmcid: 2118437
doi: 10.1084/jem.20061660
Redpath, S. A. et al. ICOS controls Foxp3+ regulatory T-cell expansion, maintenance and IL-10 production during helminth infection. Eur. J. Immunol. 43, 705–715 (2013).
pubmed: 23319295
pmcid: 3615169
doi: 10.1002/eji.201242794
Patel, A. A., Ginhoux, F. & Yona, S. Monocytes, macrophages, dendritic cells and neutrophils: an update on lifespan kinetics in health and disease. Immunology 163, 250–261 (2021).
pubmed: 33555612
pmcid: 8207393
doi: 10.1111/imm.13320
Grant, F. M. et al. BACH2 drives quiescence and maintenance of resting Treg cells to promote homeostasis and cancer immunosuppression. J. Exp. Med. 217, e20190711 (2020).
pubmed: 32515782
pmcid: 7478731
doi: 10.1084/jem.20190711
Cheng, G. et al. IL-2 Receptor Signaling Is Essential for the Development of Klrg1+ Terminally Differentiated T Regulatory Cells. J. Immunol. 189, 1780–1791 (2012).
pubmed: 22786769
doi: 10.4049/jimmunol.1103768
Booth, N. J. et al. Different Proliferative Potential and Migratory Characteristics of Human CD4+ Regulatory T Cells That Express either CD45RA or CD45RO. J. Immunol. 184, 4317–4326 (2010).
pubmed: 20231690
doi: 10.4049/jimmunol.0903781
Croese, J. et al. Experimental hookworm infection and gluten microchallenge promote tolerance in celiac disease. J. Allergy Clin. Immunol. 135, 508–516.e505 (2015).
pubmed: 25248819
doi: 10.1016/j.jaci.2014.07.022
Mantel, P. Y. et al. Molecular mechanisms underlying FOXP3 induction in human T cells. J. Immunol. 176, 3593–3602 (2006).
pubmed: 16517728
doi: 10.4049/jimmunol.176.6.3593
Gavin, M. A. et al. Single-cell analysis of normal and FOXP3-mutant human T cells: FOXP3 expression without regulatory T cell development. Proc. Natl Acad. Sci. USA 103, 6659–6664 (2006).
pubmed: 16617117
pmcid: 1458937
doi: 10.1073/pnas.0509484103
Sakaguchi, S. et al. Regulatory T Cells and Human Disease. Annu Rev. Immunol. 38, 541–566 (2020).
pubmed: 32017635
doi: 10.1146/annurev-immunol-042718-041717
Wohlfert, E. A. et al. GATA3 controls Foxp3
pubmed: 21965331
pmcid: 3204837
doi: 10.1172/JCI57456
Levine, A. G. et al. Stability and function of regulatory T cells expressing the transcription factor T-bet. Nature 546, 421–425 (2017).
pubmed: 28607488
pmcid: 5482236
doi: 10.1038/nature22360
Valkiers, S. et al. Recent advances in T-cell receptor repertoire analysis: Bridging the gap with multimodal single-cell RNA sequencing. ImmunoInformatics 5, 100009 (2022).
doi: 10.1016/j.immuno.2022.100009
Blount, D. et al. Immunologic profiles of persons recruited for a randomized, placebo-controlled clinical trial of hookworm infection. Am. J. Trop. Med. Hyg. 81, 911–916 (2009).
pubmed: 19861631
doi: 10.4269/ajtmh.2009.09-0237
Feary, J. et al. Safety of hookworm infection in individuals with measurable airway responsiveness: a randomized placebo-controlled feasibility study. Clin. Exp. Allergy 39, 1060–1068 (2009).
pubmed: 19400893
pmcid: 2728895
doi: 10.1111/j.1365-2222.2009.03187.x
Feary, J. R. et al. Experimental hookworm infection: a randomized placebo-controlled trial in asthma. Clin. Exp. Allergy 40, 299–306 (2010).
pubmed: 20030661
pmcid: 2814083
doi: 10.1111/j.1365-2222.2009.03433.x
Tanasescu, R. et al. Hookworm Treatment for Relapsing Multiple Sclerosis: A Randomized Double-Blinded Placebo-Controlled Trial. JAMA Neurol. 77, 1089–1098 (2020).
pubmed: 32539079
doi: 10.1001/jamaneurol.2020.1118
Braun, J. et al. SARS-CoV-2-reactive T cells in healthy donors and patients with COVID-19. Nature 587, 270–274 (2020).
pubmed: 32726801
doi: 10.1038/s41586-020-2598-9
Carr, E. J. et al. The cellular composition of the human immune system is shaped by age and cohabitation. Nat. Immunol. 17, 461–468 (2016).
pubmed: 26878114
pmcid: 4890679
doi: 10.1038/ni.3371
Tahapary, D. L. et al. Helminth infections and type 2 diabetes: a cluster-randomized placebo controlled SUGARSPIN trial in Nangapanda, Flores, Indonesia. BMC Infect. Dis. 15, 133 (2015).
pubmed: 25888525
pmcid: 4389675
doi: 10.1186/s12879-015-0873-4
Johnston, C. J. et al. Cultivation of Heligmosomoides polygyrus: an immunomodulatory nematode parasite and its secreted products. J. Vis. Exp. e52412, https://doi.org/10.3791/52412 (2015).
Bagwell, C. B. et al. Automated Data Cleanup for Mass Cytometry. Cytom. Part A 97, 184–198 (2020).
doi: 10.1002/cyto.a.23926
Chevrier, S. et al. Compensation of Signal Spillover in Suspension and Imaging Mass Cytometry. Cell Syst. 6, 612–620.e615 (2018).
pubmed: 29605184
pmcid: 5981006
doi: 10.1016/j.cels.2018.02.010
Van Gassen, S. et al. FlowSOM: Using self-organizing maps for visualization and interpretation of cytometry data. Cytom. Part A 87, 636–645 (2015).
doi: 10.1002/cyto.a.22625
Tibshirani, R., Walther, G. & Hastie, T. Estimating the number of clusters in a data set via the gap statistic. J. R. Stat. Soc.: Ser. B (Stat. Methodol.) 63, 411–423 (2001).
doi: 10.1111/1467-9868.00293
van Unen, V. et al. Visual analysis of mass cytometry data by hierarchical stochastic neighbour embedding reveals rare cell types. Nat. Commun. 8, 1740 (2017).
pubmed: 29170529
pmcid: 5700955
doi: 10.1038/s41467-017-01689-9
Linderman, G. C., Rachh, M., Hoskins, J. G., Steinerberger, S. & Kluger, Y. Fast interpolation-based t-SNE for improved visualization of single-cell RNA-seq data. Nat. Methods 16, 243–245 (2019).
pubmed: 30742040
pmcid: 6402590
doi: 10.1038/s41592-018-0308-4
Kobak, D. & Berens, P. The art of using t-SNE for single-cell transcriptomics. Nat. Commun. 10, https://doi.org/10.1038/s41467-019-13056-x (2019).
Pedersen, C. B. et al. cyCombine allows for robust integration of single-cell cytometry datasets within and across technologies. Nat. Commun. 13, 1698 (2022).
pubmed: 35361793
pmcid: 8971492
doi: 10.1038/s41467-022-29383-5
Wickham, H. et al. Welcome to the Tidyverse. J. Open Source Softw. 4, 1686 (2019).
doi: 10.21105/joss.01686
Gu, Z., Eils, R. & Schlesner, M. Complex heatmaps reveal patterns and correlations in multidimensional genomic data. Bioinformatics 32, 2847–2849 (2016).
pubmed: 27207943
doi: 10.1093/bioinformatics/btw313
Nowicka, M. et al. CyTOF workflow: differential discovery in high-throughput high-dimensional cytometry datasets [version 4; peer review: 2 approved]. F1000Res. 6, https://doi.org/10.12688/f1000research.11622.4 (2019).
Ritchie, M. E. et al. limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 43, e47–e47 (2015).
pubmed: 25605792
pmcid: 4402510
doi: 10.1093/nar/gkv007