Infection with Burkholderia Pseudomallei - Immune Correlates of Survival in Acute Melioidosis

Overview

Journal Sci Rep

Specialty Science

Date 2017 Sep 24

PMID 28939855

Citations 28

Authors

Susanna J Dunachie

Kemajittra Jenjaroen

Catherine J Reynolds

Kathryn J Quigley

Ruhena Sergeant

Manutsanun Sumonwiriya

Panjaporn Chaichana

Suchintana Chumseng

Pitchayanant Ariyaprasert

Patricia Lassaux

Louise Gourlay

Charuporn Promwong

Prapit Teparrukkul

Direk Limmathurotsakul

Nicholas P J Day

Daniel M Altmann

Rosemary J Boyton

Affiliations

Soon will be listed here.

Abstract

Melioidosis, caused by Burkholderia pseudomallei, is a potentially lethal infection with no licensed vaccine. There is little understanding of why some exposed individuals have no symptoms, while others rapidly progress to sepsis and death, or why diabetes confers increased susceptibility. We prospectively recruited a cohort of 183 acute melioidosis patients and 21 control subjects from Northeast Thailand and studied immune parameters in the context of survival status and the presence or absence of diabetes. HLA-B*46 (one of the commonest HLA class I alleles in SE Asia) and HLA-C*01 were associated with an increased risk of death (odds ratio 2.8 and 3.1 respectively). Transcriptomic analysis during acute infection in diabetics indicated the importance of interplay between immune pathways including those involved in antigen presentation, chemotaxis, innate and adaptive immunity and their regulation. Survival was associated with enhanced T cell immunity to nine of fifteen immunodominant antigens analysed including AhpC (BPSL2096), BopE (BPSS1525), PilO (BPSS1599), ATP binding protein (BPSS1385) and an uncharacterised protein (BPSL2520). T cell immunity to GroEL (BPSL2697) was specifically impaired in diabetic individuals. This characterization of immunity associated with survival during acute infection offers insights into correlates of protection and a foundation for design of an effective multivalent vaccine.

Citing Articles

Dysfunctional host cellular immune responses are associated with mortality in melioidosis.

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Burkholderia pseudomallei BipD modulates host mitophagy to evade killing.

Nan D, Rao C, Tang Z, Yang W, Wu P, Chen J Nat Commun. 2024; 15(1):4740.

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Deciphering the human antibody response against during melioidosis using a comprehensive immunoproteome approach.

Wagner G, Stanjek T, Albrecht D, Lipp M, Dunachie S, Foderl-Hobenreich E Front Immunol. 2023; 14:1294113.

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BurkHostGEN: a study protocol for evaluating variations in the and host genomes associated with melioidosis infection.

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