Dysfunctional host cellular immune responses are associated with mortality in melioidosis
Melioidosis is a tropical infection caused by the intracellular pathogen , an underreported and emerging global threat. As melioidosis-associated mortality is frequently high despite antibiotics, novel management strategies are critically needed. Therefore, we sought to determine whether functional...
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Published in | Emerging microbes & infections Vol. 13; no. 1; p. 2380822 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
United States
Taylor & Francis
31.12.2024
Taylor & Francis Group |
Subjects | |
Online Access | Get full text |
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Summary: | Melioidosis is a tropical infection caused by the intracellular pathogen
, an underreported and emerging global threat. As melioidosis-associated mortality is frequently high despite antibiotics, novel management strategies are critically needed. Therefore, we sought to determine whether functional changes in the host innate and adaptive immune responses are induced during acute melioidosis and are associated with outcome. Using a unique whole blood stimulation assay developed for use in resource-limited settings, we examined induced cellular functional and phenotypic changes in a cohort of patients with bacteremic melioidosis prospectively enrolled within 24 hours of positive blood culture and followed for 28 days. Compared to healthy controls, melioidosis survivors generated an IL-17 response mediated by Th17 cells and terminally-differentiated effector memory CD8
T cells (P < 0.05, both), persisting to 28-days after enrollment. Furthermore, melioidosis survivors developed polyfunctional cytokine production in CD8
T cells (P < 0.01). Conversely, a reduction in CCR6
CD4
T cells was associated with higher mortality, even after adjustments for severity of illness (P = 0.004). Acute melioidosis was also associated with a profound acute impairment in monocyte function as stimulated cytokine responses were reduced in classical, intermediate and non-classical monocytes. Impaired monocyte cytokine function improved by 28-days after enrollment. These data suggest that IL-17 mediated cellular responses may be contributors to host defense during acute melioidosis, and that innate immune function may be impaired. These insights could provide novel targets for the development of therapies and vaccine targets in this frequently lethal disease. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 T. Eoin West and Narisara Chantratita contributed equally to this study. Shelton W. Wright and Peeraya Ekchariyawat contributed equally to this study. Supplemental data for this article can be accessed online at https://doi.org/10.1080/22221751.2024.2380822. |
ISSN: | 2222-1751 2222-1751 |
DOI: | 10.1080/22221751.2024.2380822 |