HIV Infection Disrupts the Sympatric Host–Pathogen Relationship in Human Tuberculosis
Open Access
- 7 March 2013
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLoS Genetics
- Vol. 9 (3), e1003318
- https://doi.org/10.1371/journal.pgen.1003318
Abstract
The phylogeographic population structure of Mycobacterium tuberculosis suggests local adaptation to sympatric human populations. We hypothesized that HIV infection, which induces immunodeficiency, will alter the sympatric relationship between M. tuberculosis and its human host. To test this hypothesis, we performed a nine-year nation-wide molecular-epidemiological study of HIV–infected and HIV–negative patients with tuberculosis (TB) between 2000 and 2008 in Switzerland. We analyzed 518 TB patients of whom 112 (21.6%) were HIV–infected and 233 (45.0%) were born in Europe. We found that among European-born TB patients, recent transmission was more likely to occur in sympatric compared to allopatric host–pathogen combinations (adjusted odds ratio [OR] 7.5, 95% confidence interval [95% CI] 1.21–infinity, p = 0.03). HIV infection was significantly associated with TB caused by an allopatric (as opposed to sympatric) M. tuberculosis lineage (OR 7.0, 95% CI 2.5–19.1, pM. tuberculosis strains collected during a population-based study in the Canton of Bern between 1991 and 2011. In summary, these findings support a model for TB in which the stable relationship between the human host and its locally adapted M. tuberculosis is disrupted by HIV infection. Human tuberculosis (TB) caused by Mycobacterium tuberculosis kills 1.5 million people each year. M. tuberculosis has been affecting humans for millennia, suggesting that different strain lineages may be adapted to specific human populations. The combination of a particular strain lineage and its corresponding patient population can be classified as sympatric (e.g. Euro-American lineage in Europeans) or allopatric (e.g. East-Asian lineage in Europeans). We hypothesized that infection with the human immunodeficiency virus (HIV), which impairs the human immune system, will interfere with this host–pathogen relationship. We performed a nation-wide molecular-epidemiological study of HIV–infected and HIV–negative TB patients between 2000 and 2008 in Switzerland. We found that HIV infection was associated with the less adapted allopatric lineages among patients born in Europe, and this was not explained by social or other patient factors such as increased social mixing in HIV–infected individuals. Strikingly, the association between HIV infection and less adapted M. tuberculosis lineages was stronger in patients with more pronounced immunodeficiency. Our observation was replicated in a second independent panel of M. tuberculosis strains collected during a population-based study in the Canton of Bern. In summary, our study provides evidence that the sympatric host–pathogen relationship in TB is disrupted by HIV infection.This publication has 69 references indexed in Scilit:
- Old and new selective pressures on Mycobacterium tuberculosisInfection, Genetics and Evolution, 2012
- Tracking human migrations by the analysis of the distribution of HLA alleles, lineages and haplotypes in closed and open populationsPhilosophical Transactions B, 2012
- Host–pathogen coevolution in human tuberculosisPhilosophical Transactions B, 2012
- TuberculosisThe Lancet, 2011
- Host–parasite local adaptation after experimental coevolution of Caenorhabditis elegans and its microparasite Bacillus thuringiensisProceedings. Biological sciences, 2011
- Nadir CD4 T Cell Count as Predictor and High CD4 T Cell Intrinsic Apoptosis as Final Mechanism of Poor CD4 T Cell Recovery in Virologically Suppressed HIV‐Infected Patients: Clinical ImplicationsClinical Infectious Diseases, 2010
- Incomplete Peripheral CD4+Cell Count Restoration in HIV‐Infected Patients Receiving Long‐Term Antiretroviral TreatmentClinical Infectious Diseases, 2009
- Early Depletion ofMycobacterium tuberculosis–Specific T Helper 1 Cell Responses after HIV‐1 InfectionThe Journal of Infectious Diseases, 2008
- An African origin for the intimate association between humans and Helicobacter pyloriNature, 2007
- Biological and biomedical implications of the co-evolution of pathogens and their hostsNature Genetics, 2002