Commensals and immune modulation
Aim of the research
The research focuses on the communication between commensal microorganisms and the immune system, exploring how this interaction can determine health or disease outcomes. We investigates how commensals influence and guard against inflammation in the lungs and upper respiratory tract, particularly in response to allergens, viral infections or irritants. At birth, the immune system is not fully developed, requiring calibration to manage harmful pathogens and benign foreign particles. Thus, understanding how commensals fine-tune the immune system in young children is crucial.
…The research focuses on the communication between commensal microorganisms and the immune system, exploring how this interaction can determine health or disease outcomes. We investigates how commensals influence and guard against inflammation in the lungs and upper respiratory tract, particularly in response to allergens, viral infections or irritants. At birth, the immune system is not fully developed, requiring calibration to manage harmful pathogens and benign foreign particles. Thus, understanding how commensals fine-tune the immune system in young children is crucial.
We examine immunomodulation by commensals and their molecules in antigen-presenting cells (dendritic cells and macrophages) as well as regulatory T and B cells in children and adults living in transitional areas. Our focus includes helminth parasites, gut commensals, their metabolites and airborne microorganisms. To comprehend how mucosal immune responses are altered in individuals with chronic respiratory diseases (allergic rhinitis, asthma, and COPD), we analyze immune responses in respiratory mucosal tissues.
We utilize human in vitro models based on primary nasal and bronchial epithelial cells combined with immune cells to study the effects of commensals or their derivatives on mucosal immune responses. We are initiating studies involving human subjects to investigate the protective mechanisms of commensal products and develop treatment strategies aimed at preventing inflammatory diseases in the lungs.
Group members
- Hermelijn Smits (Group leader)
- Willianne Hoepel (postdoc)
- Yvonne de Visser (postdoc)
- Margarida Viola (postdoc)
- Oscar van Hengel (PhD student)
- Yu Cui (PhD student)
- Samson Folami (PhD student)
- Arifa Ozir-Fazalalikhan (senior research technician)
- Natalia Wasowska (research assistant)
Partners / Collaborators
Simon Jochems (LUCID) - respiratory viral infections and systems tissue immunology, Ron Hokke (LUCID) - molecular characteristics of helminth parasites, Maria Yazdanbakhsh (LUCID) - human studies in rural and urban areas in Indonesia and Africa, Ingrid de Visser (CHDR) - clinical studies involving metabolites and controlled rhinovirus infections, Pieter Hiemstra and Anne van der Does (LUMC Pulmonology) - mucosal models with human primary bronchial and nasal epithelial cells and respiratory viral infections, Ben Marsland (Monash University, Australia) - the role of gut metabolites in the gut-lung axis, Rick Maizels and Dr Henry McSorley (University of Glasgow and Dundee, UK) - immunemodulation by helminth parasites and their molecules, Erika von Mutius (Helmholz Institute, Munich, Germany) - the immunomodulatory role of farm dust in the airways, Markus Ege (Technical University Munich, Germany) - clinical studies with minimally processed milk in children, Gerdien Tramper (Franciscus Gasthuis, Rotterdam) - the use of bacterial lysates in protection against respiratory infections in moderate-late preterm infants, Arjen Speksnijder (Hogeschool, Leiden) - airborne biodiversity and the impact on the immune system.
Rsearch cluster
Selected publications
- Voskamp AL, Tak T, Gerdes ML, Menafra R, Duijster E, Jochems SP, Kielbasa SM, Kormelink TG, Stam KA, van Hengel ORJ, de Jong NW, Hendriks RW, Kloet SL, Yazdanbakhsh M, de Jong EC, Gerth van Wijk R, Smits HH. Inflammatory and tolerogenic myeloid cells determine outcome following human allergen challenge. J Exp Med. 2023 Sep 4;220(9):e20221111. doi: 10.1084/jem.20221111. Epub 2023 Jul 10. Erratum in: J Exp Med. 2023 Sep 4;220(9):e2022111108162023c. doi: 10.1084/jem.2022111108162023c. PMID: 37428185; PMCID: PMC10333709.
- Chayé MAM, Gasan TA, Ozir-Fazalalikhan A, Scheenstra MR, Zawistowska-Deniziak A, van Hengel ORJ, Gentenaar M, Manurung MD, Harvey MR, Codée JDC, Chiodo F, Heijke AM, Kalinowska A, van Diepen A, Hensbergen PJ, Yazdanbakhsh M, Guigas B, Hokke CH, Smits HH. Schistosoma mansoni egg-derived thioredoxin and Sm14 drive the development of IL-10 producing regulatory B cells. PLoS Negl Trop Dis. 2023 Jun 26;17(6):e0011344. doi: 10.1371/journal.pntd.0011344. PMID: 37363916; PMCID: PMC10328244.
- Roukens AHE, Pothast CR, König M, Huisman W, Dalebout T, Tak T, Azimi S, Kruize Y, Hagedoorn RS, Zlei M, Staal FJT, de Bie FJ, van Dongen JJM, Arbous SM, Zhang JLH, Verheij M, Prins C, van der Does AM, Hiemstra PS, de Vries JJC, Janse JJ, Roestenberg M, Myeni SK, Kikkert M, Yazdanbakhsh M, Heemskerk MHM, Smits HH, Jochems SP; in collaboration with BEAT-COVID group; in collaboration with COVID-19 LUMC group. Prolonged activation of nasal immune cell populations and development of tissue-resident SARS-CoV-2-specific CD8+ T cell responses following COVID-19. Nat Immunol. 2022 Jan;23(1):23-32. doi: 10.1038/s41590-021-01095-w. Epub 2021 Dec 22. PMID: 34937933.
- von Mutius E, Smits HH. Primary prevention of asthma: from risk and protective factors to targeted strategies for prevention. Lancet. 2020 Sep 19;396(10254):854-866. doi: 10.1016/S0140-6736(20)31861-4. Epub 2020 Sep 7. PMID: 32910907.
- Kuipers ME, Nolte-'t Hoen ENM, van der Ham AJ, Ozir-Fazalalikhan A, Nguyen DL, de Korne CM, Koning RI, Tomes JJ, Hoffmann KF, Smits HH, Hokke CH. DC-SIGN mediated internalisation of glycosylated extracellular vesicles from Schistosoma mansoni increases activation of monocyte-derived dendritic cells. J Extracell Vesicles. 2020 Apr 30;9(1):1753420. doi: 10.1080/20013078.2020.1753420. PMID: 32489529; PMCID: PMC7241508.