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.
Fierer
J
J
Medical and Pathology Services, VA San Diego Healthcare System, University of California, San Diego, San Diego, California, USA. jfierer@ucsd.edu
Walls
L
L
Eckmann
L
L
Yamamoto
T
T
Kirkland
T N
TN
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