Human Hookworm Infection Enhances Mycobacterial Growth Inhibition and Associates With Reduced Risk of Tuberculosis Infection

Matthew K. O'Shea1,2,3*, Thomas E. Fletcher3,4, Julius Muller1, Rachel Tanner1, Magali Matsumiya1, J. Wendi Bailey4, Jayne Jones4, Steven G. Smith5, Gavin Koh6, William G. Horsnell2,7, Nicholas J. Beeching4, James Dunbar3,8,Duncan Wilson3, Adam F. Cunningham9 and Helen McShane1

 

1Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Oxford, United Kingdom
2Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom
3Royal Centre for Defence Medicine, Joint Medical Command, Birmingham, United Kingdom
4Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, United Kingdom
5Department of Immunology and Infection, London School of Hygiene and Tropical Medicine, London, United Kingdom
6Department of Infectious Diseases, Northwick Park Hospital, London, United Kingdom
7Institute of Infectious Disease and Molecular Medicine and Division of Immunology, University of Cape Town, Cape Town, South Africa
8Department of Infectious Diseases, The Friarage Hospital, Northallerton, United Kingdom
9Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom

Abstract

Soil-transmitted helminths and Mycobacterium tuberculosis frequently coincide geographically and it is hypothesized that gastrointestinal helminth infection may exacerbate tuberculosis (TB) disease by suppression of Th1 and Th17 responses. However, few studies have focused on latent TB infection (LTBI), which predominates globally. We performed a large observational study of healthy adults migrating from Nepal to the UK (n = 645). Individuals were screened for LTBI and gastrointestinal parasite infections. A significant negative association between hookworm and LTBI-positivity was seen (OR = 0.221; p = 0.039). Hookworm infection treatment did not affect LTBI conversions. Blood from individuals with hookworm had a significantly greater ability to control virulent mycobacterial growth in vitro than from those without, which was lost following hookworm treatment. There was a significant negative relationship between mycobacterial growth and eosinophil counts. Eosinophil-associated differential gene expression characterized the whole blood transcriptome of hookworm infection and correlated with improved mycobacterial control. These data provide a potential alternative explanation for the reduced prevalence of LTBI among individuals with hookworm infection, and possibly an anti-mycobacterial role for helminth-induced eosinophils.

Keywords

Tuberculosis
Latent tuberculosis
LTBI
Hookworm
Eosinophil
Growth inhibition
Published by

Frontiers in Immunology