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.


METHODS
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.


RESULTS
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.
National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India.
Parakkal Jovvian
PJ
George
National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India.
Nathella Pavan
NP
Kumar
Government Stanley Medical Hospital, Chennai, India.
Rathinam
R
Sridhar
National Institute for Research in Tuberculosis, Chennai, India.
Luke E
LE
Hanna
National Institute for Research in Tuberculosis, Chennai, India.
Dina
D
Nair
National Institute for Research in Tuberculosis, Chennai, India.
Vaithilingam V
VV
Banurekha
Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Thomas B
TB
Nutman
National Institutes of Health-NIRT-International Center for Excellence in Research, Chennai, India; Laboratory of Parasitic Diseases, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
Subash
S
Babu
D000209:Acute-Phase Proteins / Q000378:metabolism; D000293:Adolescent; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D060085:Coinfection; D003710:Demography; D005260:Female; D006801:Humans; D007110:Immunity, Active; D007249:Inflammation / Q000276:immunology; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D017171:Strongyloides stercoralis; D013322:Strongyloidiasis / Q000150:complications* / Q000276:immunology; D014397:Tuberculosis, Pulmonary / Q000150:complications* / Q000276:immunology*; D055815:Young Adult
D000209:Acute-Phase Proteins; D015415:Biomarkers; D020782:Matrix Metalloproteinases