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Infection and Immunity, September 1998, p. 4397-4402, Vol. 66, No. 9
Medical and Pathology
Services1 and
Research
Service,
Received 17 April 1997/Returned for modification 26 May
1997/Accepted 21 June 1998
Inbred strains of mice vary in their susceptibility to
Coccidioides immitis. We infected resistant DBA/2 (D2) mice
and three susceptible strains of mice (C57BL/6 [B6], BALB/c, and
CAST/Ei) by intraperitoneal injection of arthroconidia and determined
the severity of infection based on colony counts of fungus in the spleens and lungs 14 days after infection. We used quantitative reverse
transcription-PCR to measure the amounts of cytokines made in the
spleens and lungs of infected mice. Susceptible mice made 1,000-fold
more interleukin-10 (IL-10) than resistant D2 mice and about 10-fold
more IL-4. In contrast, D2 mice had more IL-12 p40 in their lungs than
did B6 mice. Resistant and susceptible mice made equivalent amounts of
gamma interferon, IL-6, and IL-2. In order to determine whether IL-10
adversely affected the response to C. immitis, we infected
IL-10-deficient mice, and they were found to be as resistant as D2
mice. This result indicates that IL-10 plays a crucial role in
determining susceptibility to C. immitis in inbred mice.
Because IL-4 mRNA levels were higher in most strains of susceptible
mice, we also infected IL-4-deficient B6 mice. They were more resistant
than B6 controls but not as resistant as IL-10-deficient mice. Thus,
both IL-10 and IL-4 adversely affect the ability of C57BL mice to
resist infection with C. immitis, but IL-10 has a larger
effect and is the cytokine that is consistently associated with
susceptibility in all strains of inbred mice.
0019-9567/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
Importance of Interleukin-10 in Genetic
Susceptibility of Mice to Coccidioides immitis
and
*
Corresponding author. Mailing address: Infectious
Diseases Section (111F), VA San Diego Healthcare System, 3350 La Jolla
Village Dr., San Diego, CA 92161. Phone: (619) 552-7446. Fax: (619)
552-4398. E-mail: jfierer{at}ucsd.edu.
Present address: Chubu National Hospital, Obu City, Japan.
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