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Infection and Immunity, March 1999, p. 1493-1500, Vol. 67, No. 3
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Probing the Function of Bordetella
bronchiseptica Adenylate Cyclase Toxin by Manipulating Host
Immunity
Eric T.
Harvill,
Peggy A.
Cotter,
Ming Huam
Yuk, and
Jeff F.
Miller*
Department of Microbiology and Immunology,
UCLA School of Medicine, Los Angeles, California 90095-1747
Received 23 October 1998/Returned for modification 19 November
1998/Accepted 9 December 1998
We have examined the role of adenylate cyclase-hemolysin (CyaA) by
constructing an in-frame deletion in the Bordetella
bronchiseptica cyaA structural gene and comparing wild-type and
cyaA deletion strains in natural host infection models.
Both the wild-type strain RB50 and its adenylate cyclase toxin deletion
(
cyaA) derivative efficiently establish persistent
infections in rabbits, rats, and mice following low-dose inoculation.
In contrast, an inoculation protocol that seeds the lower respiratory
tract revealed significant differences in bacterial numbers and in
polymorphonuclear neutrophil recruitment in the lungs from days 5 to 12 postinoculation. We next explored the effects of disarming specific
aspects of the immune system on the relative phenotypes of wild-type
and
cyaA bacteria. SCID, SCID-beige, or
RAG-1
/
mice succumbed to lethal systemic infection
following high- or low-dose intranasal inoculation with the wild-type
strain but not the
cyaA mutant. Mice rendered
neutropenic by treatment with cyclophosphamide or by knockout mutation
in the granulocyte colony-stimulating factor locus were highly
susceptible to lethal infection by either wild-type or
cyaA strains. These results reveal the significant role
played by neutrophils early in B. bronchiseptica infection and by acquired immunity at later time points and suggest that phagocytic cells are a primary in vivo target of the
Bordetella adenylate cyclase toxin.
*
Corresponding author. Mailing address: Department of
Microbiology and Immunology, UCLA School of Medicine, Center for the Health Sciences, 10833 LeConte Ave., Los Angeles, CA 90095-1747. Phone:
(310) 206-7926. Fax: (310) 206-3865. E-mail:
jfmiller{at}ucla.edu.
Infection and Immunity, March 1999, p. 1493-1500, Vol. 67, No. 3
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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