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Title: Diabetes alters immune response patterns to acute melioidosis in humans
Authors: Barbara Kronsteiner
Panjaporn Chaichana
Manutsanun Sumonwiriya
Kemajitra Jenjaroen
Fazle Rabbi Chowdhury
Suchintana Chumseng
Prapit Teparrukkul
Direk Limmathurotsakul
Nicholas P.J. Day
Paul Klenerman
Susanna J. Dunachie
University of Oxford
Mahidol University
Nuffield Department of Clinical Medicine
Bangabandhu Sheikh Mujib Medical University
Sunpasitthiprasong Hospital
Keywords: Immunology and Microbiology;Medicine
Issue Date: 1-Jul-2019
Citation: European Journal of Immunology. Vol.49, No.7 (2019), 1092-1106
Abstract: © 2019 The Authors. European Journal of Immunology published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. Diabetes mellitus (DM) is a serious global health problem currently affecting over 450 million people worldwide. Defining its interaction with major global infections is an international public health priority. Melioidosis is caused by Burkholderia pseudomallei, an exemplar pathogen for studying intracellular bacterial infection in the context of DM due to the 12-fold increased risk in this group. We characterized immune correlates of survival in peripheral blood of acute melioidosis patients with and without DM and highlight different immune response patterns. We demonstrate the importance of circulating NK cells and show that CX3CR1 expression on lymphocytes is a novel correlate of survival from acute melioidosis. Furthermore, excessive serum levels of IL-15 and IL-18BP contribute to poor outcome independent of DM comorbidity. CD8+ T cells and granzyme B expression in NK cells are important for survival of non-DM patients, whereas high antibody titers against B. pseudomallei and double-negative T cells are linked to survival of DM patients. Recall responses support a role of γδ T-cell-derived IFN-γ in the establishment of protective immunity in the DM group. Defining the hallmarks of protection in people with DM is crucial for the design of new therapies and vaccines targeting this rapidly expanding risk group.
ISSN: 15214141
Appears in Collections:Scopus 2019

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