A critical role of interleukin-10 in the response of bovine macrophages to infection by Mycobacterium avium subsp paratuberculosis.

OBJECTIVES

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.

SAMPLE POPULATION

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

PROCEDURE

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 AND CLINICAL RELEVANCE

The capacity of M avium subsp paratuberculosis to induce IL-10 expression may be a major determinant of virulence for this organism.