Integrative immune analysis in patients with leprosy reveals host factors associated with mycobacterial controlResearch in context
Summary: Background: Leprosy is a debilitating, chronic infectious disease, ranking second after tuberculosis in the order of severe human mycobacterial diseases. If timely treatment is not initiated, infection with its causative agent, Mycobacterium leprae, can result in severe nerve damage leadin...
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Elsevier
2025-08-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396425002993 |
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| author | Anouk van Hooij Krista E. van Meijgaarden Marufa Khatun Santosh Soren Kimberley Walburg Khorshed Alam Abu Sufian Chowdhury Colette L.M. van Hees Jan Hendrik Richardus Annemieke Geluk |
| author_facet | Anouk van Hooij Krista E. van Meijgaarden Marufa Khatun Santosh Soren Kimberley Walburg Khorshed Alam Abu Sufian Chowdhury Colette L.M. van Hees Jan Hendrik Richardus Annemieke Geluk |
| author_sort | Anouk van Hooij |
| collection | DOAJ |
| description | Summary: Background: Leprosy is a debilitating, chronic infectious disease, ranking second after tuberculosis in the order of severe human mycobacterial diseases. If timely treatment is not initiated, infection with its causative agent, Mycobacterium leprae, can result in severe nerve damage leading to life-long disabilities. Host immunity largely dictates the spectral disease presentation, ranging from multi- to paucibacillary. Studying the host response to M. leprae is, however, complicated by the inability to culture this mycobacterium in vitro. Immune correlates of protection in persons at risk of leprosy are, therefore, essentially unknown. Methods: To identify host factors related to mycobacterial control, functional mycobacterial growth inhibition assays combined with extensive immunophenotyping by spectral flow cytometry were performed for patients with leprosy and their contacts. This integrative approach merged sampling of peripheral blood mononuclear cells in low resource areas with immune-analysis using cutting edge technology. Findings: In contrast to the current dogma, no intrinsic differences in mycobacterial control in vitro between patients with high and low bacillary loads were observed. Immunophenotyping at consecutive levels revealed a significant link between the induction of chemokines to mycobacterial antigens and expression of CXCR3 and CCR4 on adaptive immune cells in contacts controlling M. leprae infection. Interpretation: These results offer more detailed insights into protective immunity against M. leprae and define host factors associated with bacterial control, fuelling improved diagnosis and treatment of leprosy. Funding: Q.M. Gastmann-Wichers Foundation, the Leprosy Research Initiative & the Turing Foundation (ILEP#: 707.19.02), R2STOP; the Leprosy Mission Great Britain. |
| format | Article |
| id | doaj-art-fe52659091764ea9baacefe69f55e412 |
| institution | DOAJ |
| issn | 2352-3964 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj-art-fe52659091764ea9baacefe69f55e4122025-08-20T03:04:51ZengElsevierEBioMedicine2352-39642025-08-0111810585510.1016/j.ebiom.2025.105855Integrative immune analysis in patients with leprosy reveals host factors associated with mycobacterial controlResearch in contextAnouk van Hooij0Krista E. van Meijgaarden1Marufa Khatun2Santosh Soren3Kimberley Walburg4Khorshed Alam5Abu Sufian Chowdhury6Colette L.M. van Hees7Jan Hendrik Richardus8Annemieke Geluk9Deptartment of Infectious Diseases, LUCID, Leiden University Medical Center, the Netherlands; Corresponding author.Deptartment of Infectious Diseases, LUCID, Leiden University Medical Center, the NetherlandsResearch Program, The Leprosy Mission International Bangladesh, Nilphamari, BangladeshResearch Program, The Leprosy Mission International Bangladesh, Nilphamari, BangladeshDeptartment of Infectious Diseases, LUCID, Leiden University Medical Center, the NetherlandsResearch Program, The Leprosy Mission International Bangladesh, Nilphamari, BangladeshResearch Program, The Leprosy Mission International Bangladesh, Nilphamari, BangladeshDepartment of Dermatology, Erasmus Medical Center, Rotterdam, the NetherlandsDepartment of Public Health, Erasmus MC, University Medical Center Rotterdam, Rotterdam, the NetherlandsDeptartment of Infectious Diseases, LUCID, Leiden University Medical Center, the NetherlandsSummary: Background: Leprosy is a debilitating, chronic infectious disease, ranking second after tuberculosis in the order of severe human mycobacterial diseases. If timely treatment is not initiated, infection with its causative agent, Mycobacterium leprae, can result in severe nerve damage leading to life-long disabilities. Host immunity largely dictates the spectral disease presentation, ranging from multi- to paucibacillary. Studying the host response to M. leprae is, however, complicated by the inability to culture this mycobacterium in vitro. Immune correlates of protection in persons at risk of leprosy are, therefore, essentially unknown. Methods: To identify host factors related to mycobacterial control, functional mycobacterial growth inhibition assays combined with extensive immunophenotyping by spectral flow cytometry were performed for patients with leprosy and their contacts. This integrative approach merged sampling of peripheral blood mononuclear cells in low resource areas with immune-analysis using cutting edge technology. Findings: In contrast to the current dogma, no intrinsic differences in mycobacterial control in vitro between patients with high and low bacillary loads were observed. Immunophenotyping at consecutive levels revealed a significant link between the induction of chemokines to mycobacterial antigens and expression of CXCR3 and CCR4 on adaptive immune cells in contacts controlling M. leprae infection. Interpretation: These results offer more detailed insights into protective immunity against M. leprae and define host factors associated with bacterial control, fuelling improved diagnosis and treatment of leprosy. Funding: Q.M. Gastmann-Wichers Foundation, the Leprosy Research Initiative & the Turing Foundation (ILEP#: 707.19.02), R2STOP; the Leprosy Mission Great Britain.http://www.sciencedirect.com/science/article/pii/S2352396425002993Mycobacterial growth inhibition assaySpectral flow cytometryLeprosyImmunophenotypingBCGMycobacterium leprae |
| spellingShingle | Anouk van Hooij Krista E. van Meijgaarden Marufa Khatun Santosh Soren Kimberley Walburg Khorshed Alam Abu Sufian Chowdhury Colette L.M. van Hees Jan Hendrik Richardus Annemieke Geluk Integrative immune analysis in patients with leprosy reveals host factors associated with mycobacterial controlResearch in context EBioMedicine Mycobacterial growth inhibition assay Spectral flow cytometry Leprosy Immunophenotyping BCG Mycobacterium leprae |
| title | Integrative immune analysis in patients with leprosy reveals host factors associated with mycobacterial controlResearch in context |
| title_full | Integrative immune analysis in patients with leprosy reveals host factors associated with mycobacterial controlResearch in context |
| title_fullStr | Integrative immune analysis in patients with leprosy reveals host factors associated with mycobacterial controlResearch in context |
| title_full_unstemmed | Integrative immune analysis in patients with leprosy reveals host factors associated with mycobacterial controlResearch in context |
| title_short | Integrative immune analysis in patients with leprosy reveals host factors associated with mycobacterial controlResearch in context |
| title_sort | integrative immune analysis in patients with leprosy reveals host factors associated with mycobacterial controlresearch in context |
| topic | Mycobacterial growth inhibition assay Spectral flow cytometry Leprosy Immunophenotyping BCG Mycobacterium leprae |
| url | http://www.sciencedirect.com/science/article/pii/S2352396425002993 |
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