Importance of interleukin-10 in genetic susceptibility of mice to Coccidioides immitis.
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.
Medical and Pathology Services, VA San Diego Healthcare System, University of California, San Diego, San Diego, California, USA. jfierer@ucsd.edu
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J
Fierer
L
L
Walls
L
L
Eckmann
T
T
Yamamoto
T N
TN
Kirkland
D000818:Animals; D003045:Coccidioides / Q000276:immunology*; D003047:Coccidioidomycosis / Q000235:genetics* / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D020022:Genetic Predisposition to Disease; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D008168:Lung / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D012333:RNA, Messenger
D016207:Cytokines; D012333:RNA, Messenger; D016753:Interleukin-10