Coincident Helminth Infection Modulates Systemic Inflammation and Immune Activation in Active Pulmonary Tuberculosis.

Background: Helminth 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. Methodology: We 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 Findings: Our 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. Conclusions: Our 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. Author Summary: Helminth-induced changes in the immune system are thought to influence the outcome of secondary infections. Approximately 50–100 million people are thought to have infection by worms known as Strongyloides stercoralis, while more than 2 billion people worldwide are infected with the bacterium, Mycobacterium tuberculosis. Interestingly, there is a great degree of overlap in the geographical spread of both infections. We and others have previously shown that helminth infections induce modulation of innate and adaptive immune responses in tuberculosis. In this study, we examined whether concomitant helminth infection has a secondary effect on systemic markers of disease severity/activity in pulmonary tuberculosis. We show that helminth infection have profound effect on lowering most of the circulating parameters associated with tuberculosis pathology. We therefore, conclude that helminth infections have both beneficial and detrimental effects on the progression of tuberculosis, with the beneficial effect manifest upon development of pathology. [ABSTRACT FROM AUTHOR]