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Originally published online as doi:10.1189/jlb.0606407 on September 12, 2006

Published online before print September 12, 2006
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(Journal of Leukocyte Biology. 2006;80:1262-1271.)
© 2006 by Society for Leukocyte Biology

Exposure to Mycobacterium avium can modulate established immunity against Mycobacterium tuberculosis infection generated by Mycobacterium bovis BCG vaccination

David K. Flaherty*, Bridget Vesosky*, Gillian L. Beamer*,{dagger}, Paul Stromberg{dagger} and Joanne Turner*,1

* Departments of Internal Medicine, Division of Infectious Diseases, Center for Microbial Interface Biology, and
{dagger} Veterinary Biosciences, The Ohio State University, Columbus, Ohio, USA

1 Correspondence: The Ohio State University, 420 West 12th Avenue, Columbus, OH 43210, USA. E-mail: joanne.turner{at}osumc.edu

ABSTRACT

Mycobacterium bovis bacille Calmette Guerin (BCG), the current vaccine against infection with Mycobacterium tuberculosis, offers a variable, protective efficacy in man. It has been suggested that exposure to environmental mycobacteria can interfere with the generation of BCG-specific immunity. We hypothesized that exposure to environmental mycobacteria following BCG vaccination would interfere with established BCG immunity and reduce protective efficacy, thus modeling the guidelines for BCG vaccination within the first year of life. Mice were vaccinated with BCG and subsequently given repeated oral doses of live Mycobacterium avium to model exposure to environmental mycobacteria. The protective efficacy of BCG with and without subsequent exposure to M. avium was determined following an aerogenic challenge with M. tuberculosis. Exposure of BCG-vaccinated mice to M. avium led to a persistent increase in the number of activated T cells within the brachial lymph nodes but similar T cell activation profiles in the lungs following infection with M. tuberculosis. The capacity of BCG-vaccinated mice to reduce the bacterial load following infection with M. tuberculosis was impaired in mice that had been exposed to M. avium. Our data suggest that exposure to environmental mycobacteria can negatively impact the protection afforded by BCG. These findings are relevant for the development of a vaccine administered in regions with elevated levels of environmental mycobacteria.

Key Words: environmental mycobacteria • interference • tuberculosis • murine






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