Helminth infection and the role of altered macrophage phenotype in tuberculosis immunopathology
Author(s)
Loader, Maria Cristina
Type
Thesis
Abstract
Introduction
Tuberculosis (TB) and soil-transmitted helminths (STHs) infect ~1.7 and 1.5 billion people worldwide, predominantly in the tropics. TB has been associated with STH infection, and co-infected individuals appear to have worse lung pathology. The impact of STH infection on the innate immune response to TB is poorly understood. TB patients have elevated biomarkers of lung degradation known as matrix metalloproteinases (MMPs) and levels correlate with degree of pulmonary destruction. I investigated the relationship between TB and STH infection with particular focus on MMPs.
Methods
I recruited 61 adults with active pulmonary TB and 51 controls in Iquitos, Peru. I obtained three consecutive stool samples for copro-parasitology, sputum for TB confirmation and blood for plasma and cell-culture. ELISA and Luminex multiplex assay were used to analyse plasma and cell culture supernatant for MMP, cytokine and chemokine levels.
Results
TB was associated with STH infection (aOR 2.7, 95%CI 1.1-6.6) and strength of association increased with increasing number of STH species (3+STH aOR 4.7, 95%CI 1.01-34.45). TB infection was associated with elevated MMPs, pro-inflammatory cytokines and chemokines. STH infection was independently associated with increased plasma IgE, MMPs and some pro-inflammatory cytokines. TB-STH co-infection was asso- ciated with increased MMP-13 (861.38 vs 766.26pg/mL, p<0.05) and MMP-10 (1198.65 vs 895.57pg/mL, p<0.01) compared to TB alone.
Conclusions
These data demonstrate the positive association between TB and STH infection. Furthermore, multiplicity of STH infection increased the odds of TB positivity. Co-infection was associated with increased MMP levels compared to TB alone and increasing number of STH species identified increased the magnitude of the effect on MMP concentrations. This provides a possible mechanism for increased tissue destruction observed in TB-STH co-infection.
Tuberculosis (TB) and soil-transmitted helminths (STHs) infect ~1.7 and 1.5 billion people worldwide, predominantly in the tropics. TB has been associated with STH infection, and co-infected individuals appear to have worse lung pathology. The impact of STH infection on the innate immune response to TB is poorly understood. TB patients have elevated biomarkers of lung degradation known as matrix metalloproteinases (MMPs) and levels correlate with degree of pulmonary destruction. I investigated the relationship between TB and STH infection with particular focus on MMPs.
Methods
I recruited 61 adults with active pulmonary TB and 51 controls in Iquitos, Peru. I obtained three consecutive stool samples for copro-parasitology, sputum for TB confirmation and blood for plasma and cell-culture. ELISA and Luminex multiplex assay were used to analyse plasma and cell culture supernatant for MMP, cytokine and chemokine levels.
Results
TB was associated with STH infection (aOR 2.7, 95%CI 1.1-6.6) and strength of association increased with increasing number of STH species (3+STH aOR 4.7, 95%CI 1.01-34.45). TB infection was associated with elevated MMPs, pro-inflammatory cytokines and chemokines. STH infection was independently associated with increased plasma IgE, MMPs and some pro-inflammatory cytokines. TB-STH co-infection was asso- ciated with increased MMP-13 (861.38 vs 766.26pg/mL, p<0.05) and MMP-10 (1198.65 vs 895.57pg/mL, p<0.01) compared to TB alone.
Conclusions
These data demonstrate the positive association between TB and STH infection. Furthermore, multiplicity of STH infection increased the odds of TB positivity. Co-infection was associated with increased MMP levels compared to TB alone and increasing number of STH species identified increased the magnitude of the effect on MMP concentrations. This provides a possible mechanism for increased tissue destruction observed in TB-STH co-infection.
Version
Open Access
Date Issued
2022-08-25
Date Awarded
01/12/2022
Copyright Statement
Creative Commons Attribution NonCommercial NoDerivatives Licence
Advisor
Friedland, Jonathan
Cooke, Graham
Gilman, Robert
Cooper, Phil
Sponsor
Medical Research Council (Great Britain)
Mason Medical Research Foundation Grant
Royal Society of Tropical Medicine and Hygiene Small Grant
Grant Number
MR/N001192/1
Publisher Department
Department of Infectious Disease
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)