title: Evaluation of gamma interferon (IFN-γ)-induced protein 10 responses for detection of cattle infected with Mycobacterium bovis: comparisons to IFN-γ responses.
abstract: Gamma interferon (IFN-γ)-induced protein 10 (IP-10) has recently shown promise as a diagnostic biomarker of Mycobacterium tuberculosis infection of humans. The aim of the current study was to compare IP-10 and IFN-γ responses upon Mycobacterium bovis infection in cattle by using archived samples from two aerosol inoculation studies. In the first study (10(4) CFU M. bovis by aerosol, n = 7), M. bovis purified protein derivative (PPDb)-specific IP-10 and IFN-γ gene expression was detected as early as 29 days after challenge. PPDb-specific IP-10 and IFN-γ mRNA responses followed a similar pattern of expression over the course of this study and were highly correlated (r = 0.87). In the second study (10(5) CFU M. bovis by aerosol, n = 5), IP-10 and IFN-γ (protein) responses to mycobacterial antigens were compared following challenge. IFN-γ responses to mycobacterial antigens were detected at 29 days after challenge and were sustained during the remainder of the study. IFN-γ responses to mycobacterial antigens exceeded corresponding responses in nonstimulated cultures. IP-10 responses to mycobacterial antigens exceeded preinfection responses at 7, 29, and 63 days after challenge. In contrast to IFN-γ responses, IP-10 responses to mycobacterial antigens generally did not exceed the respective responses in nonstimulated cultures. IP-10 responses to medium alone and to mycobacterial antigens followed a similar pattern of response. Correlations between IP-10 and IFN-γ (protein) responses were modest (r ≈ 0.50 to 0.65). Taken together, these findings do not support the use of IP-10 protein as a biomarker for bovine tuberculosis using the current testing protocol and reagents; however, mRNA-based assays may be considered for further analysis.
authors.affiliation: National Animal Disease Center, Agricultural Research Service, U.S. Department of Agriculture, Ames, Iowa, USA. ray.waters@ars.usda.gov
authors.forename: W R
authors.initials: WR
authors.lastname: Waters
authors.forename: T C
authors.initials: TC
authors.lastname: Thacker
authors.forename: B J
authors.initials: BJ
authors.lastname: Nonnecke
authors.forename: M V
authors.initials: MV
authors.lastname: Palmer
authors.forename: I
authors.initials: I
authors.lastname: Schiller
authors.forename: B
authors.initials: B
authors.lastname: Oesch
authors.forename: H M
authors.initials: HM
authors.lastname: Vordermeier
authors.forename: E
authors.initials: E
authors.lastname: Silva
authors.forename: D M
authors.initials: DM
authors.lastname: Estes
mesh_terms: D000818:Animals; D002417:Cattle; D054357:Chemokine CXCL10 / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D020869:Gene Expression Profiling; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology / Q000378:metabolism*; D008297:Male; D009163:Mycobacterium bovis / Q000276:immunology*; D013223:Statistics as Topic; D014380:Tuberculosis, Bovine / Q000175:diagnosis* / Q000276:immunology*
chemical_list: D054357:Chemokine CXCL10; D007371:Interferon-gamma