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Originally published online as doi:10.1189/jlb.0707490 on October 3, 2007

Published online before print October 3, 2007
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(Journal of Leukocyte Biology. 2008;83:48-55.)
© 2008 by Society for Leukocyte Biology

Bovine monocyte TLR2 receptors differentially regulate the intracellular fate of Mycobacterium avium subsp. paratuberculosis and Mycobacterium avium subsp. avium

Douglas J. Weiss*,1, Cleverson D. Souza*, Oral A. Evanson*, Mark Sanders{dagger} and Mark Rutherford*

* Departments of Veterinary and Biomedical Science and
{dagger} College of Biological Sciences, University of Minnesota, St. Paul, Minnesota, USA

1 Correspondence: Departments of Veterinary and Biomedical Science, University of Minnesota, 1971 Commonwealth Ave., St. Paul, MN 55108, USA. E-mail: weiss005{at}umn.edu

ABSTRACT

Pathogenic mycobacterial organisms have the capacity to inhibit macrophage activation and phagosome maturation. Although the mechanism is complex, several studies have incriminated signaling through TLR2 receptors with subsequent activation of the MAPK pathway p38 (MAPKp38) and overproduction of IL-10 in the survival of pathogenic mycobacterial organisms. In the present study, we compared the response of bovine monocytes with infection by Mycobacterium avium subspecies paratuberculosis (MAP), the cause of paratuberculosis in ruminants, with the closely related organism M. avium subspecies avium (Maa), which usually does not cause disease in ruminants. Both MAP and Maa induced phosphorylation of MAPKp38 by bovine monocytes; however, addition of a blocking anti-TLR2 antibody partially prevented MAPKp38 phosphorylation of MAP-infected monocytes but not Maa-infected monocytes. Addition of anti-TLR2 antibody enhanced phagosome acidification and phagosome-lysosome fusion in MAP-containing phagosomes and enabled monocytes to kill MAP organisms. These changes were not observed in Maa-infected monocytes. The effect on phagosome maturation appears to occur independently from the previously described inhibitory effects of IL-10 on phagosome acidification and organism killing, as IL-10 production was not affected by addition of anti-TLR2 antibody to monocyte cultures. Therefore, signaling through the TLR2 receptor appears to play a role in phagosome trafficking and antimicrobial responses in MAP-infected bovine mononuclear phagocytes.

Key Words: phagosome • MAPK • cytokines • bacterial killing • innate immunity




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D. J. Weiss and C. D. Souza
REVIEW PAPER: Modulation of Mononuclear Phagocyte Function by Mycobacterium avium subsp. paratuberculosis
Vet. Pathol., November 1, 2008; 45(6): 829 - 841.
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