A critical role of interleukin-10 in the response of bovine macrophages to infection by Mycobacterium avium subsp paratuberculosis.
OBJECTIVE
To evaluate the role of interleukin (IL)-10 in the inability of monocyte-derived bovine macrophages to kill Mycobacterium avium subsp paratuberculosis organisms in vitro.


METHODS
Monocytes were obtained from healthy adult Holstein dairy cows that had negative results when tested for infection with M avium subsp paratuberculosis.


METHODS
Monocyte-derived macrophages were incubated with M avium subsp paratuberculosis for 2, 6, 24, 72, or 96 hours with or without addition of saturating concentrations of a goat anti-human IL-10 that has been documented to neutralize bovine IL-10 activity. Variables assessed included ingestion and killing of M avium subsp paratuberculosis; expression of tumor necrosis factor (TNF)-alpha, IL-12, IL-8, major histocompatability (MHC) class II, vacuolar H+ ATPase, and B cell CLL/lymphoma 2 (BCL-2); production of nitric oxide; acidification of phagosomes; and apoptosis of macrophages.


RESULTS
Neutralization of IL-10 enabled macrophages to kill 57% of M avium subsp paratuberculosis organisms within 96 hours. It also resulted in an increase in expression of TNF-alpha, IL-12, IL-8, MHC class II, and vacuolar H+ ATPase; decrease in expression of BCL-2; increase in acidification of phagosomes; apoptosis of macrophages; and production of nitric oxide.


CONCLUSIONS
The capacity of M avium subsp paratuberculosis to induce IL-10 expression may be a major determinant of virulence for this organism.
Weiss
Douglas J
DJ
Department of Veterinary PathoBiology, College of Veterinary Medicine, University of Minnesota, Saint Paul, MN 55108, USA.
Evanson
Oral A
OA
de Souza
Cleverson
C
Abrahamsen
Mitchell S
MS
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D002417:Cattle; D002418:Cattle Diseases / Q000276:immunology / Q000382:microbiology*; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology*; D018664:Interleukin-12 / Q000235:genetics / Q000276:immunology; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D016927:Mycobacterium avium subsp. paratuberculosis / Q000276:immunology*; D009573:Nitrites / Q000276:immunology; D010283:Paratuberculosis / Q000276:immunology* / Q000382:microbiology; D010588:Phagosomes / Q000276:immunology / Q000382:microbiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000276:immunology; D006180:Proton-Translocating ATPases / Q000235:genetics / Q000276:immunology; D012313:RNA / Q000737:chemistry / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
D000949:Histocompatibility Antigens Class II; D016209:Interleukin-8; D009573:Nitrites; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D012313:RNA; D006180:Proton-Translocating ATPases