Date Published: November 6, 2014
Publisher: Public Library of Science
Author(s): Parakkal Jovvian George, Nathella Pavan Kumar, Rathinam Sridhar, Luke E. Hanna, Dina Nair, Vaithilingam V. Banurekha, Thomas B. Nutman, Subash Babu, Joseph M. Vinetz. http://doi.org/10.1371/journal.pntd.0003289
Abstract: BackgroundHelminth infections are known to modulate innate and adaptive immune responses in active and latent tuberculosis (TB). However, the role of helminth infections in modulating responses associated with inflammation and immune activation (reflecting disease activity and/or severity) in TB is not known.MethodologyWe measured markers of inflammation and immune activation in active pulmonary TB individuals (ATB) with co-incidental Strongyloides stercoralis (Ss) infection. These included systemic levels of acute phase proteins, matrix metalloproteinases and their endogenous inhibitors and immune activation markers. As a control, we measured the systemic levels of the same molecules in TB-uninfected individuals (NTB) with or without Ss infection.Principal FindingsOur data confirm that ATB is associated with elevated levels of the various measured molecules when compared to those seen in NTB. Our data also reveal that co-incident Ss infection in ATB individuals is associated with significantly decreased circulating levels of acute phase proteins, matrix metalloproteinases, tissue inhibitors of matrix metalloproteinases as well as the systemic immune activation markers, sCD14 and sCD163. These changes are specific to ATB since they are absent in NTB individuals with Ss infection.ConclusionsOur data therefore reveal a profound effect of Ss infection on the markers associated with TB disease activity and severity and indicate that co-incidental helminth infections might dampen the severity of TB disease.
Partial Text: Tuberculosis is a major public health problem worldwide with nearly 10 million new cases occurring each year . Tuberculosis manifests as a disease spectrum ranging from latent infection to overt pulmonary or extra-pulmonary disease. Active TB reflects the progression from latent TB to active symptomatic disease, a progression reflecting the failure to contain the mycobacteria within granulomata . While adaptive immune responses play a major role in the pathogenesis of TB disease, it is also abundantly clear that systemic and local inflammatory and innate parameters significantly influence disease activity and severity . Commonly used markers to estimate TB disease severity and/or activity are factors that are essential for the underlying pathological process of TB disease and usually signify non-specific inflammatory processes that are reflected in increases in acute phase proteins, matrix metalloproteinases and systemic markers of immune activation .
Epidemiological and clinical studies in humans as well as experimental studies in animal models strongly indicate that helminth infections can confer protection from a variety of inflammatory diseases such as allergy, autoimmunity and inflammatory bowel disease , . The propensity of helminths to produce modulatory molecules to suppress anti-parasite and immuno-pathological responses at multiple levels renders them also with the ability to modulate host pathology during other chronic infections , . Furthermore, although helminths are typically inducers of strong Th2 responses, they also induce regulatory T cells, alternatively activated macrophages and anti-inflammatory cytokines and antibodies to suppress host – protective (and possibly pathological) pro-inflammatory responses . Thus, helminth products have been shown to modulate both Th1/Th17-mediated inflammation and Th2 dependent pathology . Recent data suggest that parasitic worms can potentially provide benefits to humans in a clinical setting, and infection with helminths or their products have shown promise as potential therapeutics for inflammatory bowel disease and other inflammatory disorders , . We and others have previously shown that helminth infections can modulate both the innate and adaptive arms of the immune system in active and latent TB . In this study, we sought to elucidate the modulatory function (if any) of a chronic helminth infection on the systemic pathological responses that characterize disease activity and severity in pulmonary TB. S. stercoralis infection is known to overlap geographically with M. tuberculosis and, more significantly, Ss infection in the mouse has been shown to impair immune responses to TB infection . Therefore, we elected to examine the interaction of Ss and M. tuberculosis at the systemic level.